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From interaction networks to interfaces, scanning intrinsically disordered regions using AlphaFold2

Author

Listed:
  • Hélène Bret

    (Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC))

  • Jinmei Gao

    (Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC))

  • Diego Javier Zea

    (Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC))

  • Jessica Andreani

    (Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC))

  • Raphaël Guerois

    (Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC))

Abstract

The revolution brought about by AlphaFold2 opens promising perspectives to unravel the complexity of protein-protein interaction networks. The analysis of interaction networks obtained from proteomics experiments does not systematically provide the delimitations of the interaction regions. This is of particular concern in the case of interactions mediated by intrinsically disordered regions, in which the interaction site is generally small. Using a dataset of protein-peptide complexes involving intrinsically disordered regions that are non-redundant with the structures used in AlphaFold2 training, we show that when using the full sequences of the proteins, AlphaFold2-Multimer only achieves 40% success rate in identifying the correct site and structure of the interface. By delineating the interaction region into fragments of decreasing size and combining different strategies for integrating evolutionary information, we manage to raise this success rate up to 90%. We obtain similar success rates using a much larger dataset of protein complexes taken from the ELM database. Beyond the correct identification of the interaction site, our study also explores specificity issues. We show the advantages and limitations of using the AlphaFold2 confidence score to discriminate between alternative binding partners, a task that can be particularly challenging in the case of small interaction motifs.

Suggested Citation

  • Hélène Bret & Jinmei Gao & Diego Javier Zea & Jessica Andreani & Raphaël Guerois, 2024. "From interaction networks to interfaces, scanning intrinsically disordered regions using AlphaFold2," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-023-44288-7
    DOI: 10.1038/s41467-023-44288-7
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    1. Kathryn Tunyasuvunakool & Jonas Adler & Zachary Wu & Tim Green & Michal Zielinski & Augustin Žídek & Alex Bridgland & Andrew Cowie & Clemens Meyer & Agata Laydon & Sameer Velankar & Gerard J. Kleywegt, 2021. "Highly accurate protein structure prediction for the human proteome," Nature, Nature, vol. 596(7873), pages 590-596, August.
    2. Patrick Bryant & Gabriele Pozzati & Arne Elofsson, 2022. "Improved prediction of protein-protein interactions using AlphaFold2," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    3. Mu Gao & Davi Nakajima An & Jerry M. Parks & Jeffrey Skolnick, 2022. "AF2Complex predicts direct physical interactions in multimeric proteins with deep learning," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    4. John Jumper & Richard Evans & Alexander Pritzel & Tim Green & Michael Figurnov & Olaf Ronneberger & Kathryn Tunyasuvunakool & Russ Bates & Augustin Žídek & Anna Potapenko & Alex Bridgland & Clemens Me, 2021. "Highly accurate protein structure prediction with AlphaFold," Nature, Nature, vol. 596(7873), pages 583-589, August.
    5. Cuihong Wan & Blake Borgeson & Sadhna Phanse & Fan Tu & Kevin Drew & Greg Clark & Xuejian Xiong & Olga Kagan & Julian Kwan & Alexandr Bezginov & Kyle Chessman & Swati Pal & Graham Cromar & Ophelia Pap, 2015. "Panorama of ancient metazoan macromolecular complexes," Nature, Nature, vol. 525(7569), pages 339-344, September.
    6. Patrick Bryant & Gabriele Pozzati & Arne Elofsson, 2022. "Author Correction: Improved prediction of protein-protein interactions using AlphaFold2," Nature Communications, Nature, vol. 13(1), pages 1-1, December.
    7. Nawsad Alam & Oriel Goldstein & Bing Xia & Kathryn A Porter & Dima Kozakov & Ora Schueler-Furman, 2017. "High-resolution global peptide-protein docking using fragments-based PIPER-FlexPepDock," PLOS Computational Biology, Public Library of Science, vol. 13(12), pages 1-20, December.
    8. Tomer Tsaban & Julia K. Varga & Orly Avraham & Ziv Ben-Aharon & Alisa Khramushin & Ora Schueler-Furman, 2022. "Harnessing protein folding neural networks for peptide–protein docking," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
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