alterlab-ligandmpnn

name	alterlab-ligandmpnn
description	Design protein sequences around bound ligands, metals, and nucleic acids with LigandMPNN (Dauparas 2023) — inverse folding that conditions on non-protein context, so binding-pocket and metal-site residues are chosen to fit the actual ligand. Use when designing a small-molecule or metal binding pocket, redesigning residues that contact a ligand/ion/nucleic acid, or doing enzyme active-site design where the substrate matters. For backbone sequence design with NO ligand/metal context prefer alterlab-proteinmpnn; to GENERATE a backbone or scaffold a functional site prefer alterlab-rfdiffusion; to validate a design by refolding prefer alterlab-alphafold; to co-fold or dock the ligand prefer alterlab-boltz or alterlab-diffdock. Part of the AlterLab Academic Skills suite.
license	MIT
allowed-tools	Read Write Edit Bash(python:*) Bash(uv:*)
compatibility	Runs LigandMPNN (`dauparas/LigandMPNN`, PyTorch) under `uv run python` via its `run.py`. Model checkpoints download once (small; no account). CPU works for typical sizes; a GPU only speeds large batches. Input is a structure containing the protein PLUS the ligand/metal/nucleic-acid atoms (e.g. a PDB with the HETATM records).
metadata	{"skill-author":"AlterLab","version":"1.0.0"}

LigandMPNN (ligand-aware sequence design)

Overview

LigandMPNN (Dauparas et al. 2023; dauparas/LigandMPNN) extends ProteinMPNN's inverse folding to condition on non-protein context — small-molecule ligands, metal ions, and nucleic acids. Because the model sees the ligand/metal atoms, the residues it designs for a binding pocket or metal site are chosen to complement what is actually bound, which plain ProteinMPNN (protein-atoms-only) cannot do.

Use it whenever the design target is a site that contacts a ligand or ion. For sequence design of a backbone with no bound context, use alterlab-proteinmpnn.

When to Use This Skill

Use this skill when the user wants to:

• Design a small-molecule binding pocket so the residues fit the ligand.
• Design a metal-coordinating site (e.g. Zn/Fe) with the ion in context.
• Redesign residues that contact a ligand, ion, or nucleic acid.
• Do enzyme active-site design where the substrate/cofactor should guide the choice.

Does NOT Trigger

Scenario	Use instead
Sequence design for a backbone with no ligand/metal context	alterlab-proteinmpnn
Generate a backbone or scaffold a functional motif	alterlab-rfdiffusion
Validate a design by refolding	alterlab-alphafold
Co-fold the protein WITH the ligand from scratch	alterlab-boltz
Dock a ligand into a fixed pocket (pose, not sequence)	alterlab-diffdock

Core Capabilities

1. Ligand-aware pocket design

# dauparas/LigandMPNN CLI — TODO(verify) flags/checkpoint names against your checkout
python run.py \
  --model_type ligand_mpnn \
  --pdb_path complex_with_ligand.pdb \
  --out_folder out/ \
  --number_of_batches 8

The input PDB must contain the ligand/metal atoms (HETATM). LigandMPNN designs pocket residues that fit that context; supply a fixed-positions/redesign spec to target only the site.