Alterlab ligandmpnn

Skill AlterLab-IEU/AlterLab-Academic-Skills/skills/bioinformatics/alterlab-ligandmpnn

239 evaluated academic Claude/agent skills across 17 research domains (bioinformatics, data science, clinical, social-science methods, Turkish academia & more). Executable eval per skill, deterministic citation verifier, research→write→review→publish pipeline, and a skill-finder front door. Claude Code, Cursor, Codex, Gemini CLI & Copilot.

Install

npx -y skills add AlterLab-IEU/AlterLab-Academic-Skills --skill alterlab-ligandmpnn

Assembled from the repository path, not quoted from the project. Check it against their README if it does not work.

What its author says it does

Copied from the file, not written here

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.

The file declares its own license as MIT. That is the author’s claim about this one file, and it is not the same thing as the license GitHub reports for the repository, which is listed with the other numbers below.

SKILL.md

4.2 KB, as published. Nobody here has run it

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.

2. Metal-site and nucleic-acid context

Provide the coordinating ion or the nucleic-acid chain in the structure so the model conditions on it — critical for metalloenzyme and DNA/RNA-binding designs.

3. Site-focused redesign

Restrict design to the residues within a shell of the ligand (redesign the pocket, keep the scaffold), analogous to ProteinMPNN's fixed-positions workflow. Verify the exact argument names for your version (TODO(verify)).

4. In the design pipeline

LigandMPNN provides the sequence step when the functional site involves a ligand: scaffold or generate the site with alterlab-rfdiffusion, design the pocket sequence here, then validate by refolding (alterlab-alphafold) and — if you need a pose/affinity — co-fold with alterlab-boltz or dock with alterlab-diffdock.

Resources

references/ligandmpnn_usage.md — install/pinning, model types, HETATM/context input, site-restricted design, and pipeline integration. Loaded on demand.

Part of the AlterLab Academic Skills suite.