ReviewProceedings of the National Academy of Sciences of the United States of America2014
The nature of protein folding pathways.
Review 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 146 papers.
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Who cites it
146 citing papers in PubMed.
- Structural Features of a Tiny Viral Protein, ORF7b of SARS-CoV-2.International journal of molecular sciences · 2026Article
- How far can you go? Extrapolating values of catalytic activity from known protein landscapes in natural and directed evolution.Chemical Society reviews · 2026Review
- Anti-fibrillation and trans-fibrillation activities of L-arginine modified magnetic nanoparticles on lysozyme.Biochemistry and biophysics reports · 2026Article
- Bridging structure and function: artificial intelligence-based modelling of kidney proteins.Nature reviews. Nephrology · 2026Review
- Proteins Inside the HSP60/HSP10 Fold Under a Constant Electric Field: Potential Implications for the Protein Folding Problem.International journal of molecular sciences · 2026Article
- Hierarchical friction memory leads to subdiffusive configurational dynamics of fast-folding proteins.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Unavailability of experimental 3D structural data on protein folding dynamics and necessity for a new generation of structure prediction methods in this context.Bioinformatics (Oxford, England) · 2026Article
- Does amyloid fibril nucleation occur at surfaces only?Biophysical journal · 2026Article
- Bridging Scales: Coarse-Grained Protein Models in Computational Biology.Advances in experimental medicine and biology · 2026Review
- A Multistate Adaptive System of Topologically Distinct Chiral Assemblies.Angewandte Chemie (International ed. in English) · 2025Article
- Computational study of terahertz-driven controllable molecular isomerization.Nature communications · 2025Article
- Pathway regulation mechanism by cotranslational protein folding.Communications chemistry · 2025Article
- From Concepts to Inhibitors: A Blueprint for Targeting Protein-Protein Interactions.Chemical reviews · 2025Review
- Pore formation by the CDTb component of the Clostridioides difficile binary toxin is CaCommunications biology · 2025Article
- MultiPassMerger: Automated data processing for multipass cyclic ion mobility HDX-MS.Protein science : a publication of the Protein Society · 2025Article
- Nonequilibrium Self-Assembly Control by the Stochastic Landscape Method.Journal of chemical information and modeling · 2025Article
- Small Heat Shock Proteins: Protein Aggregation Amelioration and Neuro- and Age-Protective Roles.International journal of molecular sciences · 2025Review
- Protein aggregates and biomolecular condensates: implications for human health and disease.Frontiers in molecular biosciences · 2025Review
- Heterogeneous folding landscapes and predetermined breaking points within a protein family.Protein science : a publication of the Protein Society · 2024Article
- Tracing the birth and intrinsic disorder of loops and domains in protein evolution.Biophysical reviews · 2024Review
86 more citing papers are in PubMed but not listed here.
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2 authors.
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Abstract
How do proteins fold, and why do they fold in that way? This Perspective integrates earlier and more recent advances over the 50-y history of the protein folding problem, emphasizing unambiguously clear structural information. Experimental results show that, contrary to prior belief, proteins are multistate rather than two-state objects. They are composed of separately cooperative foldon building blocks that can be seen to repeatedly unfold and refold as units even under native conditions. Similarly, foldons are lost as units when proteins are destabilized to produce partially unfolded equilibrium molten globules. In kinetic folding, the inherently cooperative nature of foldons predisposes the thermally driven amino acid-level search to form an initial foldon and subsequent foldons in later assisted searches. The small size of foldon units, ∼ 20 residues, resolves the Levinthal time-scale search problem. These microscopic-level search processes can be identified with the disordered multitrack search envisioned in the "new view" model for protein folding. Emergent macroscopic foldon-foldon interactions then collectively provide the structural guidance and free energy bias for the ordered addition of foldons in a stepwise pathway that sequentially builds the native protein. These conclusions reconcile the seemingly opposed new view and defined pathway models; the two models account for different stages of the protein folding process. Additionally, these observations answer the "how" and the "why" questions. The protein folding pathway depends on the same foldon units and foldon-foldon interactions that construct the native structure.
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