ArticleProceedings of the National Academy of Sciences of the United States of America2017
The case for defined protein folding pathways.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
58 citing papers in PubMed.
- Proteins Inside the HSP60/HSP10 Fold Under a Constant Electric Field: Potential Implications for the Protein Folding Problem.International journal of molecular sciences · 2026Article
- Structure of a transient protein-folding intermediate by pressure-jump NMR spectroscopy.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- AI-directed gene fusing prolongs the evolutionary half-life of synthetic gene circuits.Science advances · 2025Article
- How SecB maintains clients in a translocation competent state.Communications biology · 2025Article
- Order-to-Disorder and Disorder-to-Order Transitions of Proteins upon Binding to Phospholipid Membranes: Common Ground and Dissimilarities.Biomolecules · 2025Review
- Recent Advances in Protein Folding Pathway Prediction through Computational Methods.Current medicinal chemistry · 2024Review
- Structural Fluctuation, Relaxation, and Folding of Protein: An Approach Based on the Combined Generalized Langevin and RISM/3D-RISM Theories.Molecules (Basel, Switzerland) · 2023Review
- Pathfinder: Protein folding pathway prediction based on conformational sampling.PLoS computational biology · 2023Article
- The "Beacon" Structural Model of Protein Folding: Application for Trp-Cage in Water.Molecules (Basel, Switzerland) · 2023Article
- Protein structure and folding pathway prediction based on remote homologs recognition using PAthreader.Communications biology · 2023Article
- Deep mining of the protein energy landscape.Structural dynamics (Melville, N.Y.) · 2023Article
- The cofactor-dependent folding mechanism of Drosophila cryptochrome revealed by single-molecule pulling experiments.Nature communications · 2023Article
- Residue-based correlation between equilibrium and rate constants is an experimental formulation of the consistency principle for smooth structural changes of proteins.Biophysics and physicobiology · 2023Article
- Binding and Functional Folding (BFF): A Physiological Framework for Studying Biomolecular Interactions and Allostery.Journal of molecular biology · 2022Review
- Evolutionary adaptation of the protein folding pathway for secretability.The EMBO journal · 2022Article
- Protein folding in vitro and in the cell: From a solitary journey to a team effort.Biophysical chemistry · 2022Review
- Molten globule-like transition state of protein barnase measured with calorimetric force spectroscopy.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Exploring the folding energy landscapes of heme proteins using a hybrid AWSEM-heme model.Journal of biological physics · 2022Article
- Structural and Kinetic Views of Molecular Chaperones in Multidomain Protein Folding.International journal of molecular sciences · 2022Review
- Stem-loop formation drives RNA folding in mechanical unzipping experiments.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
Corrections and comments
- Commented on by
- Commented on by
- Commented on by
Authors and funding
2 authors.
Funding
Abstract
We consider the differences between the many-pathway protein folding model derived from theoretical energy landscape considerations and the defined-pathway model derived from experiment. A basic tenet of the energy landscape model is that proteins fold through many heterogeneous pathways by way of amino acid-level dynamics biased toward selecting native-like interactions. The many pathways imagined in the model are not observed in the structure-formation stage of folding by experiments that would have found them, but they have now been detected and characterized for one protein in the initial prenucleation stage. Analysis presented here shows that these many microscopic trajectories are not distinct in any functionally significant way, and they have neither the structural information nor the biased energetics needed to select native vs. nonnative interactions during folding. The opposed defined-pathway model stems from experimental results that show that proteins are assemblies of small cooperative units called foldons and that a number of proteins fold in a reproducible pathway one foldon unit at a time. Thus, the same foldon interactions that encode the native structure of any given protein also naturally encode its particular foldon-based folding pathway, and they collectively sum to produce the energy bias toward native interactions that is necessary for efficient folding. Available information suggests that quantized native structure and stepwise folding coevolved in ancient repeat proteins and were retained as a functional pair due to their utility for solving the difficult protein folding problem.
Indexed as
Identifiers
What OpenQuestion holds
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.