ArticleProceedings of the National Academy of Sciences of the United States of America2014
Energetically significant networks of coupled interactions within an unfolded protein.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed.
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- Knowledge Distillation of a Protein Language Model Yields a Foundational Implicit Solvent Model.ArXiv · 2026Article
- MDIntrinsicDimension: Dimensionality-Based Analysis of Collective Motions in Macromolecules from Molecular Dynamics Trajectories.Journal of chemical information and modeling · 2026Article
- The Role of the Electronic Structure during Protein Folding through Electron Density-Based Quantum Chemical Descriptors.ACS omega · 2026Article
- A Computational Perspective to Intermolecular Interactions and the Role of the Solvent on Regulating Protein Properties.Chemical reviews · 2025Review
- Pathway regulation mechanism by cotranslational protein folding.Communications chemistry · 2025Article
- Unsupervised Learning of Progress Coordinates during Weighted Ensemble Simulations: Application to NTL9 Protein Folding.Journal of chemical theory and computation · 2025Article
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- Linking Gas-Phase and Solution-Phase Protein Unfolding via Mobile Proton Simulations.Analytical chemistry · 2022Article
- Oncogenic Mutations in the DNA-Binding Domain of FOXO1 that Disrupt Folding: Quantitative Insights from Experiments and Molecular Simulations.Biochemistry · 2022Article
- GraphVAMPNet, using graph neural networks and variational approach to Markov processes for dynamical modeling of biomolecules.The Journal of chemical physics · 2022Article
- Suppressing Nonspecific Binding in Biolayer Interferometry Experiments for Weak Ligand-Analyte Interactions.ACS omega · 2022Article
- Denatured State Conformational Biases in Three-Helix Bundles Containing Divergent Sequences Localize near Turns and Helix Capping Residues.Biochemistry · 2021Article
- Understanding the Binding Transition State After the Conformational Selection Step: The Second Half of the Molecular Recognition Process Between NS1 of the 1918 Influenza Virus and Host p85β.Frontiers in molecular biosciences · 2021Article
- Adaptive Markov state model estimation using short reseeding trajectories.The Journal of chemical physics · 2020Article
- The use of consensus sequence information to engineer stability and activity in proteins.Methods in enzymology · 2020Article
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Authors and funding
6 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Unfolded and partially unfolded proteins participate in a wide range of biological processes from pathological aggregation to the regulation of normal cellular activity. Unfolded states can be populated under strongly denaturing conditions, but the ensemble which is relevant for folding, stability, and aggregation is that populated under physiological conditions. Characterization of nonnative states is critical for the understanding of these processes, yet comparatively little is known about their energetics and their structural propensities under native conditions. The standard view is that energetically significant coupled interactions involving multiple residues are generally not present in the denatured state ensemble (DSE) or in intrinsically disordered proteins. Using the N-terminal domain of the ribosomal protein L9, a small α-β protein, as an experimental model system, we demonstrate that networks of energetically significant, coupled interactions can form in the DSE of globular proteins, and can involve residues that are distant in sequence and spatially well separated in the native structure. X-ray crystallography, NMR, dynamics studies, native state pKa measurements, and thermodynamic analysis of more than 25 mutants demonstrate that residues are energetically coupled in the DSE. Altering these interactions by mutation affects the stability of the domain. Mutations that alter the energetics of the DSE can impact the analysis of cooperativity and folding, and may play a role in determining the propensity to aggregate.
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