ligandmpnn

name	ligandmpnn
description	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.
license	MIT
category	design-tools
tags	["sequence-design","inverse-folding","ligand-aware"]
source	https://github.com/adaptyvbio/protein-design-skills

LigandMPNN Ligand-Aware Design

Prerequisites

Requirement	Minimum	Recommended
Python	3.8+	3.10
GPU VRAM	8GB	16GB (T4)

How to run

Option 1: Modal (recommended)

cd biomodals
modal run modal_ligandmpnn.py \
  --pdb-path protein_ligand.pdb \
  --num-seq-per-target 16 \
  --sampling-temp 0.1

Option 2: Local

git 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

Ligand Specification

Ligand must be present as HETATM records in PDB:

HETATM  1  C1  LIG A 999  x.xxx  y.yyy  z.zzz  1.00  0.00  C

Supported: Small molecules, metals (Zn/Fe/Mg), cofactors (NAD/FAD/ATP), DNA/RNA

Decision tree

What's in your binding site?
├─ Small molecule / ligand → LigandMPNN ✓
├─ Metal ion → LigandMPNN ✓
├─ Cofactor → LigandMPNN ✓
└─ Protein only → ProteinMPNN

Troubleshooting

Error	Cause	Fix
KeyError: 'LIG'	Ligand not found	Check HETATM records
ValueError: no ligand atoms	Empty ligand	Verify atoms in PDB

Next: Structure prediction → protein-qc for filtering.