ArticleProceedings of the National Academy of Sciences of the United States of America2012
Energy landscape analysis of native folding of the prion protein yields the diffusion constant, transition path time, and rates.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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65 citing papers in PubMed.
- Factors modulating the assembly of human βNature structural & molecular biology · 2026Article
- Cooperative Native Contact Formation Facilitates Free Energy Barrier Crossing in Protein Folding.Physical review letters · 2026Article
- Single Molecule Force Spectroscopy to Probe Intermediates and Energetics of Membrane Protein Folding.Chemical reviews · 2026Review
- Different folding mechanisms in prion proteins from mammals with different disease susceptibility observed at the single-molecule level.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Energy landscape of conformational changes for a single unmodified protein.Npj biosensing · 2024Article
- Robust membrane protein tweezers reveal the folding speed limit of helical membrane proteins.eLife · 2023Article
- Visualizing the Domino-Like Prepore-to-Pore Transition of Streptolysin O by High-Speed AFM.The Journal of membrane biology · 2023Article
- The Effect of Time Resolution on Apparent Transition Path Times Observed in Single-Molecule Studies of Biomolecules.The journal of physical chemistry. B · 2022Article
- Direct observation of chaperone-modulated talin mechanics with single-molecule resolution.Communications biology · 2022Article
- On distributions of barrier crossing times as observed in single-molecule studies of biomolecules.Biophysical reports · 2021Article
- Observing the base-by-base search for native structure along transition paths during the folding of single nucleic acid hairpins.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Monitoring the binding and insertion of a single transmembrane protein by an insertase.Nature communications · 2021Article
- Force Dependence of Proteins' Transition State Position and the Bell-Evans Model.Nanomaterials (Basel, Switzerland) · 2021Article
- Out-of-Equilibrium Biophysical Chemistry: The Case for Multidimensional, Integrated Single-Molecule Approaches.The journal of physical chemistry. B · 2021Article
- Non-Markovian modeling of protein folding.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Modulation of a protein-folding landscape revealed by AFM-based force spectroscopy notwithstanding instrumental limitations.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Estimating transition path times and shapes from single-molecule photon trajectories: A simulation analysis.The Journal of chemical physics · 2021Article
- Detailed Balance Broken by Catch Bond Kinetics Enables Mechanical-Adaptation in Active Materials.Advanced functional materials · 2021Article
- Unfolded and intermediate states of PrP play a key role in the mechanism of action of an antiprion chaperone.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Pharmacological inactivation of the prion protein by targeting a folding intermediate.Communications biology · 2021Article
5 more citing papers are in PubMed but not listed here.
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7 authors.
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Abstract
Protein folding is described conceptually in terms of diffusion over a configurational free-energy landscape, typically reduced to a one-dimensional profile along a reaction coordinate. In principle, kinetic properties can be predicted directly from the landscape profile using Kramers theory for diffusive barrier crossing, including the folding rates and the transition time for crossing the barrier. Landscape theory has been widely applied to interpret the time scales for protein conformational dynamics, but protein folding rates and transition times have not been calculated directly from experimentally measured free-energy profiles. We characterized the energy landscape for native folding of the prion protein using force spectroscopy, measuring the change in extension of a single protein molecule at high resolution as it unfolded/refolded under tension. Key parameters describing the landscape profile were first recovered from the distributions of unfolding and refolding forces, allowing the diffusion constant for barrier crossing and the transition path time across the barrier to be calculated. The full landscape profile was then reconstructed from force-extension curves, revealing a double-well potential with an extended, partially unfolded transition state. The barrier height and position were consistent with the previous results. Finally, Kramers theory was used to predict the folding rates from the landscape profile, recovering the values observed experimentally both under tension and at zero force in ensemble experiments. These results demonstrate how advances in single-molecule theory and experiment are harnessing the power of landscape formalisms to describe quantitatively the mechanics of folding.
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