ArticleJournal of the American Chemical Society2012
Slow unfolded-state structuring in Acyl-CoA binding protein folding revealed by simulation and experiment.
Article in Journal of the American Chemical Society, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
66 citing papers in PubMed, 147 citations in OpenAlex.
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- Markov State Model of Solvent Features Reveals Water Dynamics in Protein-Peptide Binding.The journal of physical chemistry. B · 2023Article
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- Features of Protein Unfolding Transitions and Their Relation to Domain Topology Probed by Single-Molecule FRET.Biomolecules · 2023Article
- Folding@home: Achievements from over 20 years of citizen science herald the exascale era.Biophysical journal · 2023Review
- Folding@home: achievements from over twenty years of citizen science herald the exascale era.ArXiv · 2023Article
- Modeling Concentration-dependent Phase Separation Processes Involving Peptides and RNA via Residue-Based Coarse-Graining.Journal of chemical theory and computation · 2023Article
- Molecular mechanisms of spontaneous curvature and softening in complex lipid bilayer mixtures.Biophysical journal · 2022Article
- Molecular Insights into the Self-Assembly of Block Copolymer Suckerin Polypeptides into Nanoconfined β-Sheets.Small (Weinheim an der Bergstrasse, Germany) · 2022Article
- Unsupervised Learning Methods for Molecular Simulation Data.Chemical reviews · 2021Article
- Independent Markov decomposition: Toward modeling kinetics of biomolecular complexes.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Locomotor transitions in the potential energy landscape-dominated regime.Proceedings. Biological sciences · 2021Review
- FRET-based dynamic structural biology: Challenges, perspectives and an appeal for open-science practices.eLife · 2021Review
- Advances in the Multi-Orthogonal Folding of Single Polymer Chains into Single-Chain Nanoparticles.Polymers · 2021Review
- Protein storytelling through physics.Science (New York, N.Y.) · 2020Review
- Water as a Good Solvent for Unfolded Proteins: Folding and Collapse are Fundamentally Different.Journal of molecular biology · 2020Review
- Enhanced Molecular Dynamics Simulations of Intrinsically Disordered Proteins.Methods in molecular biology (Clifton, N.J.) · 2020Article
- Thermally versus Chemically Denatured Protein States.Biochemistry · 2019Article
- Commonly used FRET fluorophores promote collapse of an otherwise disordered protein.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 3 countries.
Funding
Abstract
Protein folding is a fundamental process in biology, key to understanding many human diseases. Experimentally, proteins often appear to fold via simple two- or three-state mechanisms involving mainly native-state interactions, yet recent network models built from atomistic simulations of small proteins suggest the existence of many possible metastable states and folding pathways. We reconcile these two pictures in a combined experimental and simulation study of acyl-coenzyme A binding protein (ACBP), a two-state folder (folding time ~10 ms) exhibiting residual unfolded-state structure, and a putative early folding intermediate. Using single-molecule FRET in conjunction with side-chain mutagenesis, we first demonstrate that the denatured state of ACBP at near-zero denaturant is unusually compact and enriched in long-range structure that can be perturbed by discrete hydrophobic core mutations. We then employ ultrafast laminar-flow mixing experiments to study the folding kinetics of ACBP on the microsecond time scale. These studies, along with Trp-Cys quenching measurements of unfolded-state dynamics, suggest that unfolded-state structure forms on a surprisingly slow (~100 μs) time scale, and that sequence mutations strikingly perturb both time-resolved and equilibrium smFRET measurements in a similar way. A Markov state model (MSM) of the ACBP folding reaction, constructed from over 30 ms of molecular dynamics trajectory data, predicts a complex network of metastable stables, residual unfolded-state structure, and kinetics consistent with experiment but no well-defined intermediate preceding the main folding barrier. Taken together, these experimental and simulation results suggest that the previously characterized fast kinetic phase is not due to formation of a barrier-limited intermediate but rather to a more heterogeneous and slow acquisition of unfolded-state structure.
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Registered trials
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.