ArticleBiochemistry2008
Microscopic reversibility of protein folding in molecular dynamics simulations of the engrailed homeodomain.
Article in Biochemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 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
30 citing papers in PubMed.
- Manipulating the Unfolded State of a Folded Protein through Site-Specific Backbone Modification.Biochemistry · 2026Article
- Neural network conditioned to produce thermophilic protein sequences can increase thermal stability.Scientific reports · 2025Article
- Implications of the unfolded state in the folding energetics of heterogeneous-backbone protein mimetics.Chemical science · 2022Article
- Thermostabilization mechanisms in thermophilic versus mesophilic three-helix bundle proteins.Journal of computational chemistry · 2022Article
- Determining Sequence-Dependent DNA Oligonucleotide Hybridization and Dehybridization Mechanisms Using Coarse-Grained Molecular Simulation, Markov State Models, and Infrared Spectroscopy.Journal of the American Chemical Society · 2021Article
- Conserved patterns and interactions in the unfolding transition state across SH3 domain structural homologues.Protein science : a publication of the Protein Society · 2021Article
- Shared unfolding pathways of unrelated immunoglobulin-like β-sandwich proteins.Protein engineering, design & selection : PEDS · 2019Article
- Do soft anions promote protein denaturation through binding interactions? A case study using ribonuclease A.RSC advances · 2019Article
- Insulin hexamer dissociation dynamics revealed by photoinduced T-jumps and time-resolved X-ray solution scattering.Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology · 2018Article
- Elucidation of the structural stability and dynamics of heterogeneous intermediate ensembles in unfolding pathway of the N-terminal domain of TDP-43.RSC advances · 2018Article
- Atomistic molecular dynamics simulations of bioactive engrailed 1 interference peptides (EN1-iPeps).Oncotarget · 2018Article
- Insights from molecular dynamics simulations for computational protein design.Molecular systems design & engineering · 2017Article
- Molecular dynamics of thermoenzymes at high temperature and pressure: a review.The protein journal · 2014Review
- REMD and umbrella sampling simulations to probe the energy barrier of the folding pathways of engrailed homeodomain.Journal of molecular modeling · 2014Article
- Structural dynamics of a mitochondrial tRNA possessing weak thermodynamic stability.Biochemistry · 2014Article
- Structural and functional consequences of cardiac troponin C L57Q and I61Q Ca(2+)-desensitizing variants.Archives of biochemistry and biophysics · 2013Article
- Using simulations to provide the framework for experimental protein folding studies.Archives of biochemistry and biophysics · 2013Review
- Promiscuous contacts and heightened dynamics increase thermostability in an engineered variant of the engrailed homeodomain.Protein engineering, design & selection : PEDS · 2013Article
- Multimolecule test-tube simulations of protein unfolding and aggregation.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- A temperature-dependent conformational change of NADH oxidase from Thermus thermophilus HB8.Proteins · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
Abstract
The principle of microscopic reversibility states that at equilibrium the number of molecules entering a state by a given path must equal those exiting the state via the same path under identical conditions or, in structural terms, that the conformations along the two pathways are the same. There has been some indirect evidence indicating that protein folding is such a process, but there have been few conclusive findings. In this study, we performed molecular dynamics simulations of an ultrafast unfolding and folding protein at its melting temperature to observe, on an atom-by-atom basis, the pathways the protein followed as it unfolded and folded within a continuous trajectory. In a total of 0.67 micros of simulation in water, we found six transient denaturing events near the melting temperature (323 and 330 K) and an additional refolding event following a previously identified unfolding event at a high temperature (373 K). In each case, unfolding and refolding transition state ensembles were identified, and they agreed well with experiment on the basis of a comparison of S and Phi values. On the basis of several structural properties, these 13 transition state ensembles agreed very well with each other and with four previously identified transition states from high-temperature denaturing simulations. Thus, not only were the unfolding and refolding transition states part of the same ensemble, but in five of the seven cases, the pathway the protein took as it unfolded was nearly identical to the subsequent refolding pathway. These events provide compelling evidence that protein folding is a microscopically reversible process. In the other two cases, the folding and unfolding transition states were remarkably similar to each other but the paths deviated.
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.