Evidence map›Paper›PMID 39192093›Full record

ArticleNature chemical biology2024

Massively parallel measurement of protein-protein interactions by sequencing using MP3-seq.

Alexandr Baryshev, Alyssa La Fleur, Benjamin Groves, Cirstyn Michel, David Baker, Ajasja Ljubetič, Georg Seelig

Abstract read
In one paragraph

Article in Nature chemical biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
–field-weighted citation impact
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

15 citing papers in PubMed.

  1. Article
  2. Article
  3. Amplicon/Protein Bead Display enables quantitativebioRxiv : the preprint server for biology · 2026
    Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Recent progress and future challenges in structure-based protein-protein interaction prediction.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  13. Beyond Dimerization: Harnessing Tetrameric Coiled-Coils for Nanostructure Assembly.Angewandte Chemie (International ed. in English) · 2025
    Article
  14. Review
  15. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors.

Alexandr Baryshev *Department of Electrical & Computer Engineering, University of Washington, Seattle, WA, USA.
Alyssa La Fleur *Paul G. Allen School of Computer Science and Engineering, University of Washington, Seattle, WA, USA.
Benjamin GrovesDepartment of Electrical & Computer Engineering, University of Washington, Seattle, WA, USA.
Cirstyn MichelDepartment of Bioengineering, University of Washington, Seattle, WA, USA.
David BakerDepartment of Bioengineering, University of Washington, Seattle, WA, USA.ORCID 0000-0001-7896-6217
Ajasja LjubetičDepartment of Biochemistry, University of Washington, Seattle, WA, USA. ajasja.ljubetic@ki.si.ORCID 0000-0002-2171-1579
Georg SeeligDepartment of Electrical & Computer Engineering, University of Washington, Seattle, WA, USA. gseelig@uw.edu.ORCID 0000-0002-3163-8782

Funding

National Science Foundation (NSF) 2312398United States Department of Defense | United States Navy | Office of Naval Research (ONR) N00014-16-1-3189U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R01GM120379
6 · The paper itself

Abstract

Protein-protein interactions (PPIs) regulate many cellular processes and engineered PPIs have cell and gene therapy applications. Here, we introduce massively parallel PPI measurement by sequencing (MP3-seq), an easy-to-use and highly scalable yeast two-hybrid approach for measuring PPIs. In MP3-seq, DNA barcodes are associated with specific protein pairs and barcode enrichment can be read by sequencing to provide a direct measure of interaction strength. We show that MP3-seq is highly quantitative and scales to over 100,000 interactions. We apply MP3-seq to characterize interactions between families of rationally designed heterodimers and to investigate elements conferring specificity to coiled-coil interactions. Lastly, we predict coiled heterodimer structures using AlphaFold-Multimer (AF-M) and train linear models on physics-based energy terms to predict MP3-seq values. We find that AF-M-based models could be valuable for prescreening interactions but experimentally measuring interactions remains necessary to rank their strengths quantitatively.

Indexed as

High-Throughput Nucleotide SequencingHumansProtein BindingProtein Interaction MappingProteinsTwo-Hybrid System TechniquesProteins

Identifiers

PMID39192093
PMCPMC11511666

What OpenQuestion holds

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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.