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Germinal

Skill FridrichMethod/awesome-skills/skills/germinal

"De novo antibody and nanobody (VHH) design with Germinal. Use this skill when: (1) Designing epitope-targeted nanobodies or scFvs, (2) Needing CDR design on a fixed framework, (3) Working on antibody-format binders rather than miniproteins.From its SKILL.md

Install
npx -y skills add FridrichMethod/awesome-skills --skill germinal

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SKILL.md

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Germinal Antibody and Nanobody Design

Germinal is an open pipeline for epitope-targeted de novo antibody and nanobody design. It hallucinates CDRs on a fixed framework, designs sequences with AbMPNN, and cofolds with a structure predictor (it downloads AlphaFold-Multimer params). Runnable through biomodals.

The biomodals author notes Germinal is finicky and suggests BoltzGen for general binder design; treat Germinal as the antibody-format option, not a default.

Prerequisites

RequirementValue
RunnerModal (biomodals)
GPUH100 (default; GPU env var)
SetupSee Getting started

How to run

git clone https://github.com/hgbrian/biomodals && cd biomodals

uv run --with modal --with PyYAML modal run modal_germinal.py \
  --target-yaml target_example.yaml \
  --max-trajectories 1 \
  --max-passing-designs 1

Key parameters

ParameterDefaultDescription
--target-yamlrequiredTarget config (target_name, target_pdb_path, target_chain, binder_chain, target_hotspots, length)
--run-typevhhvhh (nanobody) or scfv
--max-trajectories100Trajectories to run
--max-passing-designs10Stop after this many passing designs
--out-dir./out/germinalOutput directory

Target YAML

target_name: PDL1
target_pdb_path: target.pdb
target_chain: A
binder_chain: B
target_hotspots: "45,67,89"
length: 120

Decision tree

Antibody-format binder?
│
├─ Nanobody / VHH → germinal (run-type vhh) or mber
├─ scFv → germinal (run-type scfv)
└─ Miniprotein (not antibody) → binder-design (boltzgen, bindcraft, mosaic)

For VHH nanobodies, biomodals also has modal_mber.py (mBER) and modal_iggm.py (IgGM) as alternatives.

Cost

Adaptyv's own tests of these models showed Germinal costing about $1.60 per accepted design, averaged across 7 targets.

Troubleshooting

IssueCauseFix
Pipeline fails earlyMissing PyYAMLAdd --with PyYAML to the invocation
No passing designsHard epitope or low budgetRaise --max-trajectories
OOMLarge targetUse the default H100 or trim the target

Next: Validate with boltz or chai, rank with ipsae, filter with protein-qc.

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