ArticleBiophysical journal2020
Sequence-Based Prediction of Metamorphic Behavior in Proteins.
Article in Biophysical journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Fold-Switching Proteins.Annual review of biophysics · 2026Review
- Computational Identification of Potential Shape-Shifting Proteins from Structures.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Morpheus: a fragment-based algorithm to predict fold-switching behaviour in proteins across proteomes.Bioinformatics (Oxford, England) · 2025Article
- Fold-switching proteins.ArXiv · 2025Article
- Unveiling the cold reality of metamorphic proteins.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Impact of local unfolding fluctuations on the evolution of regional sequence preferences in proteins.Protein science : a publication of the Protein Society · 2025Article
- Metamorphic Proteins to Achieve Conformationally Selective Material Surface Binding.Small (Weinheim an der Bergstrasse, Germany) · 2025Article
- Temperature-dependent fold-switching mechanism of the circadian clock protein KaiB.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Proteomic Evidence for Amyloidogenic Cross-Seeding in Fibrinaloid Microclots.International journal of molecular sciences · 2024Article
- Fluid protein fold space and its implications.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023Article
- Distinguishing features of fold-switching proteins.Protein science : a publication of the Protein Society · 2023Review
- Design and characterization of a protein fold switching network.Nature communications · 2023Article
- Intrinsically disordered regions that drive phase separation form a robustly distinct protein class.The Journal of biological chemistry · 2023Article
- AlphaFold2 fails to predict protein fold switching.Protein science : a publication of the Protein Society · 2022Article
- Metamorphic proteins under a computational microscope: Lessons from a fold-switching RfaH protein.Computational and structural biotechnology journal · 2022Review
- A sequence-based method for predicting extant fold switchers that undergo α-helix ↔ β-strand transitions.Biopolymers · 2021Article
- Metamorphic proteins: the Janus proteins of structural biology.Open biology · 2021Article
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Authors and funding
4 authors.
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No grant is acknowledged in the PubMed record.
Abstract
An increasing number of proteins have been demonstrated in recent years to adopt multiple three-dimensional folds with different functions. These metamorphic proteins are characterized by having two or more folds with significant differences in their secondary structure, in which each fold is stabilized by a distinct local environment. So far, ∼90 metamorphic proteins have been identified in the Protein Databank, but we and others hypothesize that a far greater number of metamorphic proteins remain undiscovered. In this work, we introduce a computational model to predict metamorphic behavior in proteins using only knowledge of the sequence. In this model, secondary structure prediction programs are used to calculate diversity indices, which are measures of uncertainty in predicted secondary structure at each position in the sequence; these are then used to assign protein sequences as likely to be metamorphic versus monomorphic (i.e., having just one fold). We constructed a reference data set to train our classification method, which includes a novel compilation of 136 likely monomorphic proteins and a set of 201 metamorphic protein structures taken from the literature. Our model is able to classify proteins as metamorphic versus monomorphic with a Matthews correlation coefficient of ∼0.36 and true positive/true negative rates of ∼65%/80%, suggesting that it is possible to predict metamorphic behavior in proteins using only sequence information.
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