Out-of-Equilibrium Selection Pressure Enhances Inference from Protein Sequence Data
Open accessPublished version of a preprint
Abstract
Homologous proteins have similar three-dimensional structures and biological functions that shape their sequences. The resulting coevolution-driven correlations underlie methods from Potts models to lphaold, which infer protein structure and function from sequences. Using a minimal model, we show that fluctuating selection strength and the onset of new selection pressures improve coevolution-based inference of structural contacts. Our conclusions extend to realistic synthetic data and to the inference of interaction partners. Out-of-equilibrium noise arising from ubiquitous variations in natural selection thus enhances, rather than hinders, the success of inference from protein sequences.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764 · see citing works
Protein 3D Structure Computed from Evolutionary Sequence Variation
Marks, D. S., Colwell, L. J., Sheridan, R., Hopf, T. A., Pagnani, A., Zecchina, R., & Sander, C. (2011) · PLoS ONE · doi:10.1371/journal.pone.0028766 · Cited by 1,144 · see citing works
An evolution-based model for designing chorismate mutase enzymes
Russ, W. P., Figliuzzi, M., Stocker, C., Barrat-Charlaix, P., Socolich, M., Kast, P., Hilvert, D., Monasson, R., Cocco, S., Weigt, M., et al. (2020) · Science · doi:10.1126/science.aba3304 · Cited by 313 · see citing works
Flagged first, then by citations
- Authors
- Dietler, N., Malbranke, C., & Bitbol, A.-F.
- Affiliations
- SIB Swiss Institute of Bioinformatics (CH)
- Corresponding author
- Bitbol, Anne-Florence
- Venue
- Physical Review Letters
- Publisher
- American Physical Society (APS)
- Published
- 2026-03-11
- Volume
- 136
- Issue
- 10
- Pages
- 108402-108402
- ISSN
- 0031-9007 (ISSN-L)
- 1079-7114
- OpenAlex
- W7128594600
- Cited by
- 1
- References
- 3
- Citations by year
- 2026: 1
- FWCI
- 2.04
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Physical Review Letters (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- arXiv (Cornell University) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- arXiv (Cornell University)
- Funders
- European Research Council (851173)
- H2020 Research Infrastructures
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- protein coevolution, fluctuating selection, structural contacts, Potts model, protein homology, protein sequence data
- MeSH terms
- Amino Acid Sequence, Models, Genetic, Models, Molecular, Proteins, Selection, Genetic, Evolution, Molecular
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
