Evidence map›Paper›PMID 26297249›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2015

Protein folding guides disulfide bond formation.

Meng Qin, Wei Wang, D Thirumalai

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed
5.5field-weighted citation impact, top 4% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

56 citing papers in PubMed, 142 citations in OpenAlex.

  1. Review
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  3. Systematic determination of disulfide bond reduction potentials reveals a nonequilibrium redox hierarchy in cyanobacteria.Proceedings of the National Academy of Sciences of the United States of America · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 2 institutions in 2 countries.

Meng QinNational Laboratory of Solid State Microstructure, Department of Physics, and Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing 210093, China; Biophysics Program, Institute for Physical Science and Technology, University of Maryland, College Park, MD 20742.
Wei WangNational Laboratory of Solid State Microstructure, Department of Physics, and Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing 210093, China; thirum@umd.edu wangwei@nju.edu.cn.
D ThirumalaiBiophysics Program, Institute for Physical Science and Technology, University of Maryland, College Park, MD 20742 thirum@umd.edu wangwei@nju.edu.cn.
University of Maryland, College Park · USCollaborative Innovation Center of Advanced Microstructures · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The Anfinsen principle that the protein sequence uniquely determines its structure is based on experiments on oxidative refolding of a protein with disulfide bonds. The problem of how protein folding drives disulfide bond formation is poorly understood. Here, we have solved this long-standing problem by creating a general method for implementing the chemistry of disulfide bond formation and rupture in coarse-grained molecular simulations. As a case study, we investigate the oxidative folding of bovine pancreatic trypsin inhibitor (BPTI). After confirming the experimental findings that the multiple routes to the folded state contain a network of states dominated by native disulfides, we show that the entropically unfavorable native single disulfide [14-38] between Cys14 and Cys38 forms only after polypeptide chain collapse and complete structuring of the central core of the protein containing an antiparallel β-sheet. Subsequent assembly, resulting in native two-disulfide bonds and the folded state, involves substantial unfolding of the protein and transient population of nonnative structures. The rate of [14-38] formation increases as the β-sheet stability increases. The flux to the native state, through a network of kinetically connected native-like intermediates, changes dramatically by altering the redox conditions. Disulfide bond formation between Cys residues not present in the native state are relevant only on the time scale of collapse of BPTI. The finding that formation of specific collapsed native-like structures guides efficient folding is applicable to a broad class of single-domain proteins, including enzyme-catalyzed disulfide proteins.

Indexed as

AlgorithmsComputer SimulationProtein FoldingAprotininCysteineDisulfidesKineticsModels, ChemicalModels, MolecularProteinsProtein Structure, SecondaryProtein Structure, TertiaryAprotininCysteineDisulfidesProteinsdisulfide proteinsearly collapseenzyme-catalyzed foldingnative-like interactionsnonnative interactions

Identifiers

PMID26297249
PMCPMC4568676
OpenAlexW2156698698

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.