Evidence map›Paper›PMID 30538236›Full record

ArticleNature communications2018

Ultrahigh specificity in a network of computationally designed protein-interaction pairs.

Ravit Netzer, Dina Listov, Rosalie Lipsh, Orly Dym, Shira Albeck, Orli Knop, Colin Kleanthous, Sarel J Fleishman

Abstract read
In one paragraph

Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing 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

30 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Addressing epistasis in the design of protein function.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  5. Article
  6. Article
  7. Marginal specificity in protein interactions constrains evolution of a paralogous family.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  8. Computational design of BclxL inhibitors that target transmembrane domain interactions.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  9. Article
  10. A genetically encoded system for oxygen generation in living cells.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  11. Review
  12. Assessing and enhancing foldability in designed proteins.Protein science : a publication of the Protein Society · 2022
    Article
  13. Affinity of disordered protein complexes is modulated by entropy-energy reinforcement.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Review
  20. Computationally designed pyocyanin demethylase acts synergistically with tobramycin to kill recalcitrantProceedings of the National Academy of Sciences of the United States of America · 2021
    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

8 authors.

Ravit NetzerDepartment of Biomolecular Sciences, Weizmann Institute of Science, 7610001, Rehovot, Israel.
Dina ListovDepartment of Biomolecular Sciences, Weizmann Institute of Science, 7610001, Rehovot, Israel.
Rosalie LipshDepartment of Biomolecular Sciences, Weizmann Institute of Science, 7610001, Rehovot, Israel.
Orly DymStructural Proteomics Unit, Weizmann Institute of Science, 7610001, Rehovot, Israel.
Shira AlbeckStructural Proteomics Unit, Weizmann Institute of Science, 7610001, Rehovot, Israel.
Orli KnopDepartment of Biomolecular Sciences, Weizmann Institute of Science, 7610001, Rehovot, Israel.
Colin KleanthousDepartment of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK.ORCID http://orcid.org/0000-0002-3273-0302
Sarel J FleishmanDepartment of Biomolecular Sciences, Weizmann Institute of Science, 7610001, Rehovot, Israel. sarel@weizmann.ac.il.ORCID http://orcid.org/0000-0003-3177-7560

Funding

Biotechnology and Biological Sciences Research Council BB/E011306/1European Research Council 335439
6 · The paper itself

Abstract

Protein networks in all organisms comprise homologous interacting pairs. In these networks, some proteins are specific, interacting with one or a few binding partners, whereas others are multispecific and bind a range of targets. We describe an algorithm that starts from an interacting pair and designs dozens of new pairs with diverse backbone conformations at the binding site as well as new binding orientations and sequences. Applied to a high-affinity bacterial pair, the algorithm results in 18 new ones, with cognate affinities from pico- to micromolar. Three pairs exhibit 3-5 orders of magnitude switch in specificity relative to the wild type, whereas others are multispecific, collectively forming a protein-interaction network. Crystallographic analysis confirms design accuracy, including in new backbones and polar interactions. Preorganized polar interaction networks are responsible for high specificity, thus defining design principles that can be applied to program synthetic cellular interaction networks of desired affinity and specificity.

Indexed as

AlgorithmsBacterial ProteinsBinding SitesComputational BiologyDatabases, ProteinProtein BindingProtein Interaction MappingBacterial Proteins

Identifiers

PMID30538236
PMCPMC6290019

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.