Evidence map›Paper›PMID 33722011›Full record

ArticleThe Journal of chemical physics2021

Unfolding bovine α-lactalbumin with T-jump: Characterizing disordered intermediates via time-resolved x-ray solution scattering and molecular dynamics simulations.

Darren J Hsu, Denis Leshchev, Irina Kosheleva, Kevin L Kohlstedt, Lin X Chen

Abstract read
In one paragraph

Article in The Journal of chemical physics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing 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

17 citing papers in PubMed.

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  6. Influence of divalent metal cations on α-lactalbumin fibril formation.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2024
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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

5 authors.

Darren J HsuDepartment of Chemistry, Northwestern University, Evanston, Illinois 60208, USA.ORCID 0000000203537626
Denis LeshchevDepartment of Chemistry, Northwestern University, Evanston, Illinois 60208, USA.ORCID 0000000280493671
Irina KoshelevaCenter for Advanced Radiation Sources, The University of Chicago, Chicago, Illinois 60637, USA.ORCID 0000000295990371
Kevin L KohlstedtDepartment of Chemistry, Northwestern University, Evanston, Illinois 60208, USA.ORCID 0000000180450930
Lin X ChenDepartment of Chemistry, Northwestern University, Evanston, Illinois 60208, USA.ORCID 0000000284506687

Funding

Electric Field-stimulated Protein MechanicsP41GM118217 · NIGMS · UNIVERSITY OF CHICAGO · PI RANGANATHAN, RAMA · 2019 to 2021
$5.3M
Molecular Biophysics Training Program at Northwestern UniversityT32GM008382 · NIGMS · NORTHWESTERN UNIVERSITY · PI RADHAKRISHNAN, ISHWAR · 1990 to 2020
$4.3M
Capturing Transient Protein Structures on Multiple Spatial and Temporal ScalesR01GM115761 · NIGMS · NORTHWESTERN UNIVERSITY · PI CHEN, LIN X · 2015 to 2023
$3.0M
BioCARS: A Synchrotron Structure Biology ResourceR24GM111072 · NIGMS · UNIVERSITY OF CHICAGO · PI MOFFAT, JOHN KEITH · 2013 to 2016
$2.3M
NIGMS NIH HHS P41 GM118217NIGMS NIH HHS R01 GM115761NIGMS NIH HHS R24 GM111072NIGMS NIH HHS T32 GM008382
6 · The paper itself

Abstract

The protein folding process often proceeds through partially folded transient states. Therefore, a structural understanding of these disordered states is crucial for developing mechanistic models of the folding process. Characterization of unfolded states remains challenging due to their disordered nature, and incorporating multiple methods is necessary. Combining the time-resolved x-ray solution scattering (TRXSS) signal with molecular dynamics (MD), we are able to characterize transient partially folded states of bovine α-lactalbumin, a model system widely used for investigation of molten globule states, during its unfolding triggered by a temperature jump. We track the unfolding process between 20 µs and 70 ms and demonstrate that it passes through three distinct kinetic states. The scattering signals associated with these transient species are then analyzed with TRXSS constrained MD simulations to produce protein structures that are compatible with the input signals. Without utilizing any experimentally extracted kinetic information, the constrained MD simulation successfully drove the protein to an intermediate molten globule state; signals for two later disordered states are refined to terminal unfolded states. From our examination of the structural characteristics of these disordered states, we discuss the implications disordered states have on the folding process, especially on the folding pathway. Finally, we discuss the potential applications and limitations of this method.

Indexed as

AnimalsCattleKineticsLactalbuminMolecular Dynamics SimulationProtein ConformationProtein UnfoldingTemperatureX-Ray DiffractionLactalbumin

Identifiers

PMID33722011
PMCPMC7943248

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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.