ArticleNature communications2023
Evolutionary selection of proteins with two folds.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed.
- The intrinsic disorder challenge for AlphaFold: A case study of G3BP1 and pathogenic peptide.iScience · 2026Article
- Fold-Switching Proteins.Annual review of biophysics · 2026Review
- Disentangling coevolutionary constraints for modeling protein conformational heterogeneity.Communications chemistry · 2026Article
- Article
- Article
- A Structural Landscape Depiction of Dynamic Stability Centers of Local Structure in Protein Thermostability Engineering.Research (Washington, D.C.) · 2026Article
- Rapid estimation of protein folding pathways from sequence alone using AlphaFold2.Nature communications · 2025Article
- Morpheus: a fragment-based algorithm to predict fold-switching behaviour in proteins across proteomes.Bioinformatics (Oxford, England) · 2025Article
- Mapping the energy landscape of a fold-switching protein MAD2.Protein science : a publication of the Protein Society · 2025Article
- Memorization bias impacts modeling of alternative conformational states of solute carrier membrane proteins with methods from deep learning.PLoS computational biology · 2025Article
- Evolutionary Constraints Guide AlphaFold2 in Predicting Alternative Conformations and Inform Rational Mutation Design.Journal of chemical information and modeling · 2025Article
- Fold-switching proteins.ArXiv · 2025Article
- Large-scale predictions of alternative protein conformations by AlphaFold2-based sequence association.Nature communications · 2025Article
- Memorization Bias Impacts Modeling of Alternative Conformational States of Symmetric Solute Carrier Membrane Proteins with Methods from Deep Learning.bioRxiv : the preprint server for biology · 2025Article
- AlphaFold2's training set powers its predictions of some fold-switched conformations.Protein science : a publication of the Protein Society · 2025Article
- Emerging frontiers in protein structure prediction following the AlphaFold revolution.Journal of the Royal Society, Interface · 2025Review
- Evolving concepts of the protein universe.iScience · 2025Review
- Sequence clustering confounds AlphaFold2.Nature · 2025Article
- Proteins with alternative folds reveal blind spots in AlphaFold-based protein structure prediction.Current opinion in structural biology · 2025Review
- Proteins with alternative folds reveal blind spots in AlphaFold-based protein structure prediction.ArXiv · 2024Article
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2 authors.
Funding
Abstract
Although most globular proteins fold into a single stable structure, an increasing number have been shown to remodel their secondary and tertiary structures in response to cellular stimuli. State-of-the-art algorithms predict that these fold-switching proteins adopt only one stable structure, missing their functionally critical alternative folds. Why these algorithms predict a single fold is unclear, but all of them infer protein structure from coevolved amino acid pairs. Here, we hypothesize that coevolutionary signatures are being missed. Suspecting that single-fold variants could be masking these signatures, we developed an approach, called Alternative Contact Enhancement (ACE), to search both highly diverse protein superfamilies-composed of single-fold and fold-switching variants-and protein subfamilies with more fold-switching variants. ACE successfully revealed coevolution of amino acid pairs uniquely corresponding to both conformations of 56/56 fold-switching proteins from distinct families. Then, we used ACE-derived contacts to (1) predict two experimentally consistent conformations of a candidate protein with unsolved structure and (2) develop a blind prediction pipeline for fold-switching proteins. The discovery of widespread dual-fold coevolution indicates that fold-switching sequences have been preserved by natural selection, implying that their functionalities provide evolutionary advantage and paving the way for predictions of diverse protein structures from single sequences.
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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.