Evidence map›Paper›PMID 38225382›Full record

ArticleMolecular systems biology2024

Systematic discovery of protein interaction interfaces using AlphaFold and experimental validation.

Chop Yan Lee, Dalmira Hubrich, Julia K Varga, Christian Schäfer, Mareen Welzel, Eric Schumbera, Milena Djokic, Joelle M Strom, Jonas Schönfeld, Johanna L Geist and 6 more

Open access · goldAbstract read
In one paragraph

Article in Molecular systems biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed
17.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

69 citing papers in PubMed, 77 citations in OpenAlex.

  1. Article
  2. Molecular dockingDigital discovery · 2026
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  5. From Thanatos to transcription: the emerging biology of THAP proteins.Cellular and molecular life sciences : CMLS · 2026
    Review
  6. Article
  7. Review
  8. Review
  9. Article
  10. Article
  11. Article
  12. Alphafuser: a parsimonious approach to predicting higher-order protein complexes.Acta crystallographica. Section D, Structural biology · 2026
    Article
  13. Article
  14. Proteome-wide prediction of interactions between structured domains and peptide motifs reveals functionally coherent subnetworks.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  15. Article
  16. Article
  17. Review
  18. Review
  19. Article
  20. Review

9 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 4 institutions in 2 countries.

Chop Yan Lee *Institute of Molecular Biology (IMB) gGmbH, 55128, Mainz, Germany.ORCID http://orcid.org/0000-0002-8907-6831
Dalmira Hubrich *Institute of Molecular Biology (IMB) gGmbH, 55128, Mainz, Germany.ORCID http://orcid.org/0000-0002-0552-2890
Julia K Varga *Department of Microbiology and Molecular Genetics, Institute for Biomedical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, 9112001, Israel.ORCID http://orcid.org/0000-0002-5318-2798
Christian SchäferInstitute of Molecular Biology (IMB) gGmbH, 55128, Mainz, Germany.ORCID http://orcid.org/0000-0002-9840-2870
Mareen WelzelInstitute of Molecular Biology (IMB) gGmbH, 55128, Mainz, Germany.
Eric SchumberaInstitute of Molecular Biology (IMB) gGmbH, 55128, Mainz, Germany.
Milena DjokicInstitute of Molecular Biology (IMB) gGmbH, 55128, Mainz, Germany.
Joelle M StromInstitute of Molecular Biology (IMB) gGmbH, 55128, Mainz, Germany.ORCID http://orcid.org/0009-0005-9094-7453
Jonas SchönfeldInstitute of Molecular Biology (IMB) gGmbH, 55128, Mainz, Germany.ORCID http://orcid.org/0000-0001-8625-0913
Johanna L GeistInstitute of Molecular Biology (IMB) gGmbH, 55128, Mainz, Germany.
Feyza PolatInstitute of Molecular Biology (IMB) gGmbH, 55128, Mainz, Germany.
Toby J GibsonStructural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, 69117, Germany.ORCID http://orcid.org/0000-0003-0657-5166
Claudia Isabelle Keller ValsecchiInstitute of Molecular Biology (IMB) gGmbH, 55128, Mainz, Germany.
Manjeet KumarStructural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, 69117, Germany.
Ora Schueler-FurmanDepartment of Microbiology and Molecular Genetics, Institute for Biomedical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, 9112001, Israel. ora.furman-schueler@mail.huji.ac.il.ORCID http://orcid.org/0000-0002-1624-0362
Katja LuckInstitute of Molecular Biology (IMB) gGmbH, 55128, Mainz, Germany. k.luck@imb-mainz.de.ORCID http://orcid.org/0000-0003-2336-9225
Institute of Molecular Biology · DEEuropean Molecular Biology Laboratory · DEHebrew University of Jerusalem · ILMammazentrum Hamburg · DE

Funding

European Union Horizon 2020 UBIMOTIF programme 860517German Research Foundation LU 2568/1-1German Research Foundation SFB1551 464588647Israel Science Foundation (ISF) 301/2021Ministry of Science and Health (MWG), Rhineland Palatinate TB-Nr.:3658/19
6 · The paper itself

Abstract

Structural resolution of protein interactions enables mechanistic and functional studies as well as interpretation of disease variants. However, structural data is still missing for most protein interactions because we lack computational and experimental tools at scale. This is particularly true for interactions mediated by short linear motifs occurring in disordered regions of proteins. We find that AlphaFold-Multimer predicts with high sensitivity but limited specificity structures of domain-motif interactions when using small protein fragments as input. Sensitivity decreased substantially when using long protein fragments or full length proteins. We delineated a protein fragmentation strategy particularly suited for the prediction of domain-motif interfaces and applied it to interactions between human proteins associated with neurodevelopmental disorders. This enabled the prediction of highly confident and likely disease-related novel interfaces, which we further experimentally corroborated for FBXO23-STX1B, STX1B-VAMP2, ESRRG-PSMC5, PEX3-PEX19, PEX3-PEX16, and SNRPB-GIGYF1 providing novel molecular insights for diverse biological processes. Our work highlights exciting perspectives, but also reveals clear limitations and the need for future developments to maximize the power of Alphafold-Multimer for interface predictions.

Indexed as

Carrier ProteinsProteinsHumansMembrane ProteinsCarrier ProteinsGIGYF1 protein, humanMembrane ProteinsPEX16 protein, humanProteinsAlphaFoldBenchmarkingExperimental ValidationLinear MotifsProtein Interaction Interface Prediction

Identifiers

PMID38225382
PMCPMC10883280
OpenAlexW4390876228

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.