ArticleProceedings of the National Academy of Sciences of the United States of America2008
Theoretical and experimental demonstration of the importance of specific nonnative interactions in protein folding.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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53 citing papers in PubMed.
- Importance of Inter-residue Contacts for Understanding Protein Folding and Unfolding Rates, Remote Homology, and Drug Design.Molecular biotechnology · 2025Review
- Gadolinium-Based NMR Spin Relaxation Measurements of Near-Surface Electrostatic Potentials of Biomolecules.Journal of the American Chemical Society · 2024Article
- Targeting the protein folding transition state by mutation: Large scale (un)folding rate accelerations without altering native stability.Protein science : a publication of the Protein Society · 2024Article
- Crowding-induced protein destabilization in the absence of soft attractions.Biophysical journal · 2022Article
- An Unusual Aspartic Acid Cluster in the Reovirus Attachment Fiber σ1 Mediates Stability at Low pH and Preserves Trimeric Organization.Journal of virology · 2022Article
- Slow Folding of a Helical Protein: Large Barriers, Strong Internal Friction, or a Shallow, Bumpy Landscape?The journal of physical chemistry. B · 2020Article
- Effects of Topology and Sequence in Protein Folding Linked via Conformational Fluctuations.Biophysical journal · 2020Article
- Size and topology modulate the effects of frustration in protein folding.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Disordered linkers in multidomain allosteric proteins: Entropic effect to favor the open state or enhanced local concentration to favor the closed state?Protein science : a publication of the Protein Society · 2018Article
- Nonnative Energetic Frustrations in Protein Folding at Residual Level: A Simulation Study of Homologous Immunoglobulin-likeInternational journal of molecular sciences · 2018Article
- On the folding of a structurally complex protein to its metastable active state.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Evidence for the principle of minimal frustration in the evolution of protein folding landscapes.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Quantifying Nonnative Interactions in the Protein-Folding Free-Energy Landscape.Biophysical journal · 2016Article
- Theoretical Insights into the Biophysics of Protein Bi-stability and Evolutionary Switches.PLoS computational biology · 2016Article
- Conformations of a Metastable SH3 Domain Characterized by smFRET and an Excluded-Volume Polymer Model.Biophysical journal · 2016Article
- Constructing sequence-dependent protein models using coevolutionary information.Protein science : a publication of the Protein Society · 2016Article
- Native contact density and nonnative hydrophobic effects in the folding of bacterial immunity proteins.PLoS computational biology · 2015Article
- The hydrophobic temperature dependence of amino acids directly calculated from protein structures.PLoS computational biology · 2015Article
- Multiscale modeling of a conditionally disordered pH-sensing chaperone.Journal of molecular biology · 2015Article
- Protein unfolding rates correlate as strongly as folding rates with native structure.Protein science : a publication of the Protein Society · 2015Article
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Authors and funding
7 authors.
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Abstract
Many experimental and theoretical studies have suggested a significant role for nonnative interactions in protein folding pathways, but the energetic contributions of these interactions are not well understood. We have addressed the energetics and the position specificity of nonnative hydrophobic interactions by developing a continuum coarse-grained chain model with a native-centric potential augmented by sequence-dependent hydrophobic interactions. By modeling the effect of different hydrophobicity values at various positions in the Fyn SH3 domain, we predicted energetically significant nonnative interactions that led to acceleration or deceleration of the folding rate depending on whether they were more populated in the transition state or unfolded state. These nonnative contacts were centered on position 53 in the Fyn SH3 domain, which lies in an exposed position in a 3(10)-helix. The energetic importance of the predicted nonnative interactions was confirmed experimentally by folding kinetics studies combined with double mutant thermodynamic cycles. By attaining agreement of theoretical and experimental investigations, this study provides a compelling demonstration that specific nonnative interactions can significantly influence folding energetics. Moreover, we show that a coarse-grained model with a simple consideration of hydrophobicity is sufficient for the accurate prediction of kinetically important nonnative interactions.
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