ArticleProceedings of the National Academy of Sciences of the United States of America2017
Evidence for the principle of minimal frustration in the evolution of protein folding landscapes.
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 31 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
31 citing papers in PubMed, 71 citations in OpenAlex.
- Article
- Tightly Knotted Enzymes Inhibit Protein-Protein Aggregation.bioRxiv : the preprint server for biology · 2026Article
- Support field neural representation learner framework for learning stability landscapes in molecular geometry.npj biomedical innovations · 2025Article
- Trp101-Mediated Cold Adaptation inACS omega · 2025Article
- Mapping the energy landscape of a fold-switching protein MAD2.Protein science : a publication of the Protein Society · 2025Article
- Multi-Modal Topology-Aware Graph Neural Network for Robust Chemical-Protein Interaction Prediction.International journal of molecular sciences · 2025Article
- Thr-to-Ala Mutation Leads to a Larger Aromatic Pair and Reduced Packing Density in α1,α3-Helices during Thioredoxin Cold Adaptation.ACS omega · 2024Article
- Surface frustration re-patterning underlies the structural landscape and evolvability of fungal orphan candidate effectors.Nature communications · 2023Article
- Electronegative clusters modulate folding status and RNA binding of unstructured RNA-binding proteins.Protein science : a publication of the Protein Society · 2023Article
- Release of frustration drives corneal amyloid disaggregation by brain chaperone.Communications biology · 2023Article
- Illuminating the "Twilight Zone": Advances in Difficult Protein Modeling.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Enhanced statistical sampling reveals microscopic complexity in the talin mechanosensor folding energy landscape.Nature physics · 2023Article
- Probing the origin of prion protein misfolding via reconstruction of ancestral proteins.Protein science : a publication of the Protein Society · 2022Article
- Evolution of frustrated and stabilising contacts in reconstructed ancient proteins.European biophysics journal : EBJ · 2021Article
- Evolution, folding, and design of TIM barrels and related proteins.Current opinion in structural biology · 2021Review
- Anomalous structural dynamics of minimally frustrated residues in cardiac troponin C triggers hypertrophic cardiomyopathy.Chemical science · 2021Article
- Article
- Energy Landscapes of Deoxyxylo- and Xylo-Nucleic Acid Octamers.The journal of physical chemistry. B · 2020Article
- Integrated Computational Approaches and Tools forAllosteric Drug Discovery.International journal of molecular sciences · 2020Review
- Energetic dependencies dictate folding mechanism in a complex protein.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
Corrections and comments
- Commented on by
- Commented on by
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Theoretical and experimental studies have firmly established that protein folding can be described by a funneled energy landscape. This funneled energy landscape is the result of foldable protein sequences evolving following the principle of minimal frustration, which allows proteins to rapidly fold to their native biologically functional conformations. For a protein family with a given functional fold, the principle of minimal frustration suggests that, independent of sequence, all proteins within this family should fold with similar rates. However, depending on the optimal living temperature of the organism, proteins also need to modulate their thermodynamic stability. Consequently, the difference in thermodynamic stability should be primarily caused by differences in the unfolding rates. To test this hypothesis experimentally, we performed comprehensive thermodynamic and kinetic analyses of 15 different proteins from the thioredoxin family. Eight of these thioredoxins were extant proteins from psychrophilic, mesophilic, or thermophilic organisms. The other seven protein sequences were obtained using ancestral sequence reconstruction and can be dated back over 4 billion years. We found that all studied proteins fold with very similar rates but unfold with rates that differ up to three orders of magnitude. The unfolding rates correlate well with the thermodynamic stability of the proteins. Moreover, proteins that unfold slower are more resistant to proteolysis. These results provide direct experimental support to the principle of minimal frustration hypothesis.
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.