Evidence map›Paper›PMID 37499032›Full record

ArticleScience (New York, N.Y.)2023

Deploying synthetic coevolution and machine learning to engineer protein-protein interactions.

Aerin Yang, Kevin M Jude, Ben Lai, Mason Minot, Anna M Kocyla, Caleb R Glassman, Daisuke Nishimiya, Yoon Seok Kim, Sai T Reddy, Aly A Khan and 1 more

Abstract read
In one paragraph

Article in Science (New York, N.Y.), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing 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

21 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. Predicting Protein-Protein Interactions from Machine-Learned Representations.Advances in experimental medicine and biology · 2026
    Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Review
  17. Addressing epistasis in the design of protein function.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  18. Computational tools for plant genomics and breeding.Science China. Life sciences · 2024
    Review
  19. Assessing the functional roles of coevolving PHD finger residues.Protein science : a publication of the Protein Society · 2024
    Article
  20. Article
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

11 authors.

Aerin YangDepartment of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA.ORCID 0000-0002-8704-0288
Kevin M JudeDepartment of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA.ORCID 0000-0002-3675-5136
Ben LaiToyota Technological Institute at Chicago, Chicago, IL 60637, USA.
Mason MinotDepartment of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.ORCID 0000-0003-0225-9107
Anna M KocylaDepartment of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA.ORCID 0000-0002-0258-4551
Caleb R GlassmanDepartment of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA.ORCID 0000-0002-3342-7989
Daisuke NishimiyaDepartment of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA.ORCID 0000-0002-3529-5916
Yoon Seok KimDepartment of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA.ORCID 0000-0003-3332-0652
Sai T ReddyDepartment of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.ORCID 0000-0002-9177-0857
Aly A KhanToyota Technological Institute at Chicago, Chicago, IL 60637, USA.ORCID 0000-0003-3933-8538
K Christopher GarciaDepartment of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA.ORCID 0000-0001-9273-0278

Funding

A Synchrotron Radiation Structural Biology ResourcesP30GM133894 · NIGMS · STANFORD UNIVERSITY · PI Ritimukta Sarangi · 2020 to 2026
$43.3M
A Global Map of Interactions Among Human Cell Surface Proteins and Secreted LigandsR01GM150125 · NIGMS · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI GARCIA, KENAN CHRISTOPHER, THOMSON, MATTHEW W. · 2022 to 2025
$11.3M
Howard Hughes Medical InstituteNIGMS NIH HHS P30 GM133894NIGMS NIH HHS R01 GM150125
6 · The paper itself

Abstract

Fine-tuning of protein-protein interactions occurs naturally through coevolution, but this process is difficult to recapitulate in the laboratory. We describe a platform for synthetic protein-protein coevolution that can isolate matched pairs of interacting muteins from complex libraries. This large dataset of coevolved complexes drove a systems-level analysis of molecular recognition between Z domain-affibody pairs spanning a wide range of structures, affinities, cross-reactivities, and orthogonalities, and captured a broad spectrum of coevolutionary networks. Furthermore, we harnessed pretrained protein language models to expand, in silico, the amino acid diversity of our coevolution screen, predicting remodeled interfaces beyond the reach of the experimental library. The integration of these approaches provides a means of simulating protein coevolution and generating protein complexes with diverse molecular recognition properties for biotechnology and synthetic biology.

Indexed as

Directed Molecular EvolutionProtein Interaction Domains and MotifsProteinsAmino AcidsDatasets as TopicMachine LearningStaphylococcal Protein AAmino AcidsProteinsStaphylococcal Protein A

Identifiers

PMID37499032
PMCPMC10403280

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.