Evidence map›Paper›PMID 40131954›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2025

Prediction of phase-separation propensities of disordered proteins from sequence.

Sören von Bülow, Giulio Tesei, Fatima Kamal Zaidi, Tanja Mittag, Kresten Lindorff-Larsen

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing 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

49 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
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  6. AF-CALVADOS: AlphaFold-guided simulations of multi-domain proteins at the proteome level.Protein science : a publication of the Protein Society · 2026
    Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Distinguishing near- versus off-critical phase behaviors of intrinsically disordered proteins.Reports on progress in physics. Physical Society (Great Britain) · 2026
    Article
  12. amyloid-predict and LLPS-predict: Predicting phase separation propensities in the intrinsically disordered proteome.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  13. Article
  14. Condensates as Conformation Editors of Disordered Client Proteins.Journal of the American Chemical Society · 2026
    Article
  15. Review
  16. Article
  17. Review
  18. Article
  19. Generative design of intrinsically disordered protein regions with IDiom.bioRxiv : the preprint server for biology · 2026
    Article
  20. Investigating Phase Separation in Genome Folding via Multiscale Computational Modeling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
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

5 authors.

Sören von BülowDepartment of Biology, Structural Biology and NMR Laboratory, Linderstrøm-Lang Centre for Protein Science, University of Copenhagen, Copenhagen 2200, Denmark.ORCID 0000-0001-7125-5973
Giulio TeseiDepartment of Biology, Structural Biology and NMR Laboratory, Linderstrøm-Lang Centre for Protein Science, University of Copenhagen, Copenhagen 2200, Denmark.ORCID 0000-0003-4339-4460
Fatima Kamal ZaidiDepartment of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN 38105.
Tanja MittagDepartment of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN 38105.ORCID 0000-0002-1827-3811
Kresten Lindorff-LarsenDepartment of Biology, Structural Biology and NMR Laboratory, Linderstrøm-Lang Centre for Protein Science, University of Copenhagen, Copenhagen 2200, Denmark.ORCID 0000-0002-4750-6039

Funding

Understanding the Sequence and Structural Determinants of Phase Behavior of ALS-Causing ProteinsR01NS121114 · NINDS · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI Tanja Mittag, ROHIT V PAPPU · 2021 to 2026
$3.8M
American Lebanese Syrian Associated Charities (ALSAC) NAEuropean Molecular Biology Organization (EMBO) ALTF 810-2022HHS | National Institutes of Health (NIH) R01NS121114NINDS NIH HHS R01 NS121114Novo Nordisk Fonden (NNF) NNF18OC0032608Novo Nordisk Fonden (NNF) NNF18OC0033950
6 · The paper itself

Abstract

Phase separation is one possible mechanism governing the selective cellular enrichment of biomolecular constituents for processes such as transcriptional activation, mRNA regulation, and immune signaling. Phase separation is mediated by multivalent interactions of macromolecules including intrinsically disordered proteins and regions (IDRs). Despite considerable advances in experiments, theory, and simulations, the prediction of the thermodynamics of IDR phase behavior remains challenging. We combined coarse-grained molecular dynamics simulations and active learning to develop a fast and accurate machine learning model to predict the free energy and saturation concentration for phase separation directly from sequence. We validate the model using computational and previously measured experimental data, as well as new experimental data for six proteins. We apply our model to all 27,663 IDRs of chain length up to 800 residues in the human proteome and find that 1,420 of these (5%) are predicted to undergo homotypic phase separation with transfer free energies < -2

Indexed as

Intrinsically Disordered ProteinsHumansHydrophobic and Hydrophilic InteractionsMachine LearningMolecular Dynamics SimulationThermodynamicsIntrinsically Disordered Proteinsbiophysicaldisordered proteinsphase separationproteins

Identifiers

PMID40131954
PMCPMC12002312

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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.