kūkulu - Diffusion-Based Reconstruction of Antibody CDR Loops using a Structure-Aware Joint Embedding Predictive Architecture

Silico Biosciences

Usage

from kukulu import generate
import json

result = generate(
    checkpoint_path="checkpoint.pt",
    pdb_path="1ABC.pdb",
    h_chain="H",
    l_chain="L",
    antigen_chains="A|B",
    device="cuda"
)

print(json.dumps(result, indent=4))

Benchmarking

scripts/evaluate/generate_benchmark_structures.py generates CDR designs for every .pdb file in paper/benchmarks/pdb/, scores each one with HADDOCK3, and writes the results into a new workbook copied from paper/benchmarks/antibody_benchmarks.xlsx (the template sheet itself is never modified). Chain IDs (H/L/antigen) are looked up automatically from the Reference PDBs sheet by matching the pdb filename against its pdb_id.

python scripts/evaluate/generate_benchmark_structures.py \
    --checkpoint .model/kukulu_20260728_001.pt \
    --pdb_dir paper/benchmarks/pdb \
    --template_xlsx paper/benchmarks/antibody_benchmarks.xlsx \
    --output_xlsx paper/benchmarks/antibody_benchmark_complete.xlsx \
    --n 5 \
    --device cpu

Requires hmmscan (HMMER, used by the legacy ANARCI numbering backend) and haddock3-score on PATH in addition to the Python dependencies.

paper/benchmarks/report.qmd renders a Quarto dashboard (score distributions per target, a sortable results table) from antibody_benchmark_complete.xlsx. Re-render it after generating new benchmark data:

cd paper/benchmarks
QUARTO_PYTHON=../../.venv/bin/python quarto render report.qmd

Citing Us

If you use the Kukulu model, the prepared/masked structural data, or build upon our work, we'd love for you to cite us.

• Rabinowitz, S., Nigam, P., Santolla, N., & Ford, C. T. (2026). Kukulu: Diffusion-Based Reconstruction of Antibody CDR Loops using a Structure-Aware Joint Embedding Predictive Architecture [Preprint]. bioRxiv. doi: 10.64898/2026.08.03.742168

@article {Rabinowitz2026.08.03.742168,
	author = {Rabinowitz, Seth and Nigam, Prbhuv and Santolla, Nicholas and Ford, Colby T.},
	title = {{Kukulu: Diffusion-Based Reconstruction of Antibody CDR Loops using a Structure-Aware Joint Embedding Predictive Architecture}},
	elocation-id = {2026.08.03.742168},
	year = {2026},
	doi = {10.64898/2026.08.03.742168},
	publisher = {Cold Spring Harbor Laboratory},
	URL = {https://www.biorxiv.org/content/early/2026/08/04/2026.08.03.742168},
	eprint = {https://www.biorxiv.org/content/early/2026/08/04/2026.08.03.742168.full.pdf},
	journal = {bioRxiv}
}