Evidence map›Paper›PMID 40595555›Full record

ArticleNature communications2025

Large-scale predictions of alternative protein conformations by AlphaFold2-based sequence association.

Myeongsang Lee, Joseph W Schafer, Jeshuwin Prabakaran, Devlina Chakravarty, Madeleine F Clore, Lauren L Porter

Abstract read
In one paragraph

Article in Nature communications, 2025. 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. Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Article
  8. Article
  9. Fold-Switching Proteins.Annual review of biophysics · 2026
    Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. A dramatic protein fold switch powers a bactericidal nanomachine.bioRxiv : the preprint server for biology · 2026
    Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. 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

6 authors.

Myeongsang Lee *National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, 20894, USA.ORCID http://orcid.org/0000-0003-2078-6023
Joseph W Schafer *National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, 20894, USA.
Jeshuwin PrabakaranNational Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, 20894, USA.
Devlina ChakravartyNational Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, 20894, USA.
Madeleine F CloreNational Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, 20894, USA.ORCID http://orcid.org/0009-0005-2515-860X
Lauren L PorterNational Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, 20894, USA. porterll@nih.gov.ORCID http://orcid.org/0000-0003-2031-8326

Funding

U.S. Department of Health & Human Services | NIH | U.S. National Library of Medicine (NLM) LM202011
6 · The paper itself

Abstract

The many successes of AlphaFold2 (AF2) have inspired methods to predict multiple protein conformations, many of which have biological significance. These methods often assume that AF2 relies on evolutionary couplings to predict alternative protein conformations, but they perform poorly on fold-switching proteins, which remodel their secondary structures and modulate their functions in response to cellular stimuli. Here we present a method designed to leverage AF2's learning of protein structure more than evolutionary couplings. This method-called CF-random-outperforms other methods for predicting alternative conformations of not only fold switchers but also dozens of other proteins that undergo rigid body motions and local conformational rearrangements. It also enables predictions of fold-switched assemblies unpredicted by AlphaFold3. Several lines of evidence suggest that CF-random sometimes works by sequence association: relating patterns  from homologous sequences to a learned structural landscape. Through a blind search of thousands of Escherichia coli proteins, CF-random suggests that up to 5% switch folds.

Indexed as

Computational BiologyEscherichia coli ProteinsProtein ConformationProteinsAlgorithmsAmino Acid SequenceEscherichia coliModels, MolecularProtein FoldingProtein Structure, SecondaryEscherichia coli ProteinsProteins

Identifiers

PMID40595555
PMCPMC12219334

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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.