Temperature Dependence of Intrinsically Disordered Proteins in Simulations: What are We Missing?

S. Jephthah; L. Staby; B. B. Kragelund; M. Skepö

doi:10.1021/acs.jctc.8b01281

Temperature Dependence of Intrinsically Disordered Proteins in Simulations: What are We Missing?

S. Jephthah, L. Staby, B. B. Kragelund, M. Skepö

University of Copenhagen

Research output: Contribution to journal › Article › peer-review

Abstract

The temperature dependence of the conformational properties in simulations of the intrinsically disordered model protein histatin 5 has been investigated using different combinations of force fields, water models, and atomistic and coarse-grained methods. The results have been compared to experimental data obtained from NMR, SAXS, and CD experiments to assess the accuracy and validity of the simulations. The results showed that neither simulations completely agreed with the experimental data, nor did they agree with each other. It was however possible to conclude that the observed conformational changes upon variations in temperature were not at all driven by electrostatic interactions. The final conclusion was that none of the simulations that were investigated in this study was able to accurately capture the temperature induced conformational changes of our model IDP.

Original language	English
Pages (from-to)	2672-2683
Number of pages	12
Journal	Journal of Chemical Theory and Computation
Volume	15
Issue number	4
DOIs	https://doi.org/10.1021/acs.jctc.8b01281
Publication status	Published - 2019

Subject classification (UKÄ)

Theoretical Chemistry (including Computational Chemistry)

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10.1021/acs.jctc.8b01281

1 Doctoral Thesis (compilation)
1 Licentiate Thesis

Fighting microbial infections with force fields: Evaluating conformational ensembles of intrinsically disordered proteins
Jephthah, S., 2021, Lund: Lund University. 214 p.
Research output: Thesis › Doctoral Thesis (compilation)

Open Access
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Two aspects of simulating disorder
Jephthah, S., 2019 Apr 15, Lund: Lund University. 94 p.
Research output: Thesis › Licentiate Thesis

Cite this

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title = "Temperature Dependence of Intrinsically Disordered Proteins in Simulations: What are We Missing?",

abstract = "The temperature dependence of the conformational properties in simulations of the intrinsically disordered model protein histatin 5 has been investigated using different combinations of force fields, water models, and atomistic and coarse-grained methods. The results have been compared to experimental data obtained from NMR, SAXS, and CD experiments to assess the accuracy and validity of the simulations. The results showed that neither simulations completely agreed with the experimental data, nor did they agree with each other. It was however possible to conclude that the observed conformational changes upon variations in temperature were not at all driven by electrostatic interactions. The final conclusion was that none of the simulations that were investigated in this study was able to accurately capture the temperature induced conformational changes of our model IDP.",

author = "S. Jephthah and L. Staby and Kragelund, {B. B.} and M. Skep{\"o}",

year = "2019",

doi = "10.1021/acs.jctc.8b01281",

language = "English",

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journal = "Journal of Chemical Theory and Computation",

issn = "1549-9618",

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T1 - Temperature Dependence of Intrinsically Disordered Proteins in Simulations

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AU - Jephthah, S.

AU - Staby, L.

AU - Kragelund, B. B.

AU - Skepö, M.

PY - 2019

Y1 - 2019

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AB - The temperature dependence of the conformational properties in simulations of the intrinsically disordered model protein histatin 5 has been investigated using different combinations of force fields, water models, and atomistic and coarse-grained methods. The results have been compared to experimental data obtained from NMR, SAXS, and CD experiments to assess the accuracy and validity of the simulations. The results showed that neither simulations completely agreed with the experimental data, nor did they agree with each other. It was however possible to conclude that the observed conformational changes upon variations in temperature were not at all driven by electrostatic interactions. The final conclusion was that none of the simulations that were investigated in this study was able to accurately capture the temperature induced conformational changes of our model IDP.

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DO - 10.1021/acs.jctc.8b01281

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JO - Journal of Chemical Theory and Computation

JF - Journal of Chemical Theory and Computation

IS - 4

ER -

Temperature Dependence of Intrinsically Disordered Proteins in Simulations: What are We Missing?

Abstract

Subject classification (UKÄ)

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Research output

Fighting microbial infections with force fields: Evaluating conformational ensembles of intrinsically disordered proteins

Two aspects of simulating disorder

Cite this