Evidence map›Paper›PMID 27851936›Full record

ArticleBiophysical journal2016

Hidden Markov Modeling with Detailed Balance and Its Application to Single Protein Folding.

Yongli Zhang, Junyi Jiao, Aleksander A Rebane

Abstract read
In one paragraph

Article in Biophysical journal, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
–field-weighted citation impact
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

29 citing papers in PubMed.

  1. Single-molecule dissection of CFTR folding defects and pharmacological rescue.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
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  6. Review
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  9. Increasing the accuracy of single-molecule data analysis using tMAVEN.bioRxiv : the preprint server for biology · 2024
    Article
  10. Article
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  12. A dynamic template complex mediates Munc18-chaperoned SNARE assembly.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  13. Energetics, kinetics, and pathways of SNARE assembly in membrane fusion.Critical reviews in biochemistry and molecular biology · 2022
    Review
  14. Polybasic Patches in Both C2 Domains of Synaptotagmin-1 Are Required for Evoked Neurotransmitter Release.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022
    Article
  15. Article
  16. Article
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  18. Quantitative Models of Lipid Transfer and Membrane Contact Formation.Contact (Thousand Oaks (Ventura County, Calif.)) · 2022
    Article
  19. Article
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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.

Yongli ZhangDepartment of Cell Biology, School of Medicine, Yale University, New Haven, Connecticut. Electronic address: yongli.zhang@yale.edu.
Junyi JiaoDepartment of Cell Biology, School of Medicine, Yale University, New Haven, Connecticut; Integrated Graduate Program in Physical and Engineering Biology, Yale University, New Haven, Connecticut.
Aleksander A RebaneDepartment of Cell Biology, School of Medicine, Yale University, New Haven, Connecticut; Integrated Graduate Program in Physical and Engineering Biology, Yale University, New Haven, Connecticut; Department of Physics, Yale University, New Haven, Connecticut; Nanobiology Institute, Yale University, West Haven, Connecticut.

Funding

Skill Development for Diverse Scientific Careers: A New Course Predoctoral Program in Cellular and Molecular BiologyT32GM007223 · NIGMS · YALE UNIVERSITY · PI BASERGA, SUSAN J · 1985 to 2019
$31.0M
Single-molecule manipulation of SNAREsR01GM093341 · NIGMS · YALE UNIVERSITY · PI ZHANG, YONGLI · 2010 to 2018
$3.1M
NIGMS NIH HHS R01 GM093341NIGMS NIH HHS T32 GM007223
6 · The paper itself

Abstract

Hidden Markov modeling (HMM) has revolutionized kinetic studies of macromolecules. However, results from HMM often violate detailed balance when applied to the transitions under thermodynamic equilibrium, and the consequence of such violation has not been well understood. Here, to our knowledge, we developed a new HMM method that satisfies detailed balance (HMM-DB) and optimizes model parameters by gradient search. We used free energy of stable and transition states as independent fitting parameters and considered both normal and skew normal distributions of the measurement noise. We validated our method by analyzing simulated extension trajectories that mimicked experimental data of single protein folding from optical tweezers. We then applied HMM-DB to elucidate kinetics of regulated SNARE zippering containing degenerate states. For both simulated and measured trajectories, we found that HMM-DB significantly reduced overfitting of short trajectories compared to the standard HMM based on an expectation-maximization algorithm, leading to more accurate and reliable model fitting by HMM-DB. We revealed how HMM-DB could be conveniently used to derive a simplified energy landscape of protein folding. Finally, we extended HMM-DB to correct the baseline drift in single-molecule trajectories. Together, we demonstrated an efficient, versatile, and reliable method of HMM for kinetics studies of macromolecules under thermodynamic equilibrium.

Indexed as

Markov ChainsModels, MolecularProtein FoldingKineticsThermodynamics

Identifiers

PMID27851936
PMCPMC5112951

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.