Supporting repository for "Uncovering the flexibility of CDR loops in antibodies and TCRs through large-scale molecular dynamics" (2025).

📝 About

Supporting repository for the manuscript "Uncovering the flexibility of CDR loops in antibodies and TCRs through large-scale molecular dynamics" (Cagiada M., Spoendlin F.C., et al., bioRxiv 2025).

This repository provides notebooks, data, and analysis scripts to reproduce the figures presented in the manuscript. Additionally, the repository includes CV3-Fv pipeline scripts for implementing our setup in CALVADOS 3 (COMING SOON...).

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🗂️ Repository layout

The contents of this repository allow you to reproduce the results and figures that appear in the manuscript.

• notebooks: Contains Jupyter notebooks used to perform the analyses and generate the figures included in the manuscript
• src: Contains all datasets and supplementary files necessary for running the analysis notebooks and reproducing the results.
• figures: Includes figures generated as outputs from the analysis notebooks.
• cv3-pipeline: (coming soon): Scripts and instructions for reproducing our CV3-Fv molecular dynamics simulation setup.

N.B.: due to their large size, the all-atom simulations used in this analysis are not included in the current repository. Simulations can be found at: https://doi.org/10.5281/zenodo.17525665.

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⚙️ CV3-Fv pipeline

To run CV3-Fv simulations follow the steps below

1. Install environments

To install the required Conda environments, run:

scripts/setup_envs.sh

2. Run simulations

Simulations can be executed using:

scripts/run_sim.sh <NAME> <INSTRUC> <CHAINH> <CHAINL> <OUTDIR>

Required Arguments • NAME – Unique name for the run • INSTRUC – Path to input structure file • CHAINH – Heavy chain ID • CHAINL – Light chain ID • OUTDIR – Output directory path

3. Convert to all atom

python scripts/convert2all_atom.py --simulation_dir <DIR> --pdb_id <NAME> --h_chain <CHAINH> --l_chain <CHAINL>

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📚 Data

• CV3-Fv simulations for experimentally resolved structures from the FlAbDab database are accessible through the dedicated webserver https://opig.stats.ox.ac.uk/webapps/flabdab.
• FlAbDab and FTCRDab simulations for experimentally resolved structures can also be downloaded as from Zenodo https://doi.org/10.5281/zenodo.17552276.
• Ensembles of representative structures for all the antibodies in FlAbDab, which were predicted using ABodyBuilder2, are available on Zenodo https://doi.org/10.5281/zenodo.17555649.
• All-atom MD simulations for the two antibodies and one TCR, along with associated metadata, are available at: https://doi.org/10.5281/zenodo.17525665.

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📝 Reference this work

If you use our model please cite:

Cagiada, M., Spoendlin, F.C., Ifashe K. & Deane C.M (2025). Uncovering the flexibility of CDR loops in antibodies and TCRs through large-scale molecular dynamics. In bioRxiv (p.). https://doi.org/

@ARTICLE{Cagiada2025-cv,
  title    = "Uncovering the flexibility of CDR loops in antibodies and TCRs through large-scale molecular dynamics",
  author   = "Cagiada, Matteo and Spoendlin, Fabian. C. and Ifashe, King and Deane, Charlotte M.",
  journal  = "bioRxiv",
  pages    = "",
  month    =  ,
  year     =  2025,
  language = "en"

Also if you use the CALVADOS 3 suite for our CV3-Fv setup, please cite:

• von Bülow, S., Yasuda, I., Cao, F., Schulze, T. K., Trolle, A. I., Rauh, A. S., Crehuet, R., Lindorff-Larsen, K., & Tesei, G. (2025). Software package for simulations using the coarse-grained CALVADOS model. In arXiv [q-bio.BM]. arXiv. http://arxiv.org/abs/2504.10408

🙌 Acknowledgements

The research was supported by a Novo Nordisk Foundation Postdoctoral Fellowship (NNF23OC0082912) awarded to MC, by research funding from the UK Engineering and Physical Sciences Research Council (EPSCR) [Grant number EP/S024093/1], Roche and the Royal Commission for the Exhibition of 1851 awarded to FS and KI.

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📜 License

This project is licensed under the MIT License. See LICENSE for details.

📬 Contact

For questions or support with this repository, please use the GitHub issue tab or reach out to us via email:

📧 Matteo Cagiada: [email protected] / [email protected]

📧 Charlotte M. Deane: [email protected]