ArticleNature2010
Experimental evidence for a frustrated energy landscape in a three-helix-bundle protein family.
Article in Nature, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed.
- Coupled Binding and Folding of NS2B/NS3 Protease and Linker Effects Revealed by Topology-Based Modeling.The journal of physical chemistry. B · 2026Article
- Coupled Binding and Folding of NS2B/NS3 Protease and Linker Effects Revealed by Topology-based Modeling.bioRxiv : the preprint server for biology · 2026Article
- Article
- Massively parallel genetic perturbation suggests the energetic structure of an amyloid-β transition state.Science advances · 2025Article
- Electrostatics and hydrophobicity in the dynamics of intrinsically disordered proteins.The European physical journal. E, Soft matter · 2023Article
- Enhancing Conformational Sampling for Intrinsically Disordered and Ordered Proteins by Variational Autoencoder.International journal of molecular sciences · 2023Article
- Folding and Evolution of a Repeat Protein on the Ribosome.Frontiers in molecular biosciences · 2022Article
- Diffusion of a disordered protein on its folded ligand.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Does Electric Friction Matter in Living Cells?The journal of physical chemistry. B · 2021Article
- Slow Folding of a Helical Protein: Large Barriers, Strong Internal Friction, or a Shallow, Bumpy Landscape?The journal of physical chemistry. B · 2020Article
- Cotranslational folding cooperativity of contiguous domains of α-spectrin.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Friction-Limited Folding of Disulfide-Reduced Monomeric SOD1.Biophysical journal · 2020Article
- Slow Transition Path Times Reveal a Complex Folding Barrier in a Designed Protein.Frontiers in chemistry · 2020Article
- Dystrophin As a Molecular Shock Absorber.ACS nano · 2018Article
- Origin of Internal Friction in Disordered Proteins Depends on Solvent Quality.The journal of physical chemistry. B · 2018Article
- Transition path times of coupled folding and binding reveal the formation of an encounter complex.Nature communications · 2018Article
- Nonnative Energetic Frustrations in Protein Folding at Residual Level: A Simulation Study of Homologous Immunoglobulin-likeInternational journal of molecular sciences · 2018Article
- Butane dihedral angle dynamics in water is dominated by internal friction.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Topologically knotted deubiquitinases exhibit unprecedented mechanostability to withstand the proteolysis by an AAA+ protease.Scientific reports · 2018Article
- Transition Path Times Measured by Single-Molecule Spectroscopy.Journal of molecular biology · 2018Review
10 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Energy landscape theory is a powerful tool for understanding the structure and dynamics of complex molecular systems, in particular biological macromolecules. The primary sequence of a protein defines its free-energy landscape and thus determines the folding pathway and the rate constants of folding and unfolding, as well as the protein's native structure. Theory has shown that roughness in the energy landscape will lead to slower folding, but derivation of detailed experimental descriptions of this landscape is challenging. Simple folding models show that folding is significantly influenced by chain entropy; proteins in which the contacts are local fold quickly, owing to the low entropy cost of forming stabilizing, native contacts during folding. For some protein families, stability is also a determinant of folding rate constants. Where these simple metrics fail to predict folding behaviour, it is probable that there are features in the energy landscape that are unusual. Such general observations cannot explain the folding behaviour of the R15, R16 and R17 domains of alpha-spectrin. R15 folds approximately 3,000 times faster than its homologues, although they have similar structures, stabilities and, as far as can be determined, transition-state stabilities. Here we show that landscape roughness (internal friction) is responsible for the slower folding and unfolding of R16 and R17. We use chimaeric domains to demonstrate that this internal friction is a property of the core, and suggest that frustration in the landscape of the slow-folding spectrin domains may be due to misdocking of the long helices during folding. Theoretical studies have suggested that rugged landscapes will result in slower folding; here we show experimentally that such a phenomenon directly influences the folding kinetics of a 'normal' protein, that is, one with a significant energy barrier that folds on a relatively slow, millisecond-second, timescale.
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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.