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Title: Equilibrium denaturation and preferential interactions of an RNA tetraloop with urea

Abstract

Urea is an important organic cosolute with implications in maintaining osmotic stress in cells and differentially stabilizing ensembles of folded biomolecules. We report an equilibrium study of urea-induced denaturation of a hyperstable RNA tetraloop through unbiased replica exchange molecular dynamics. We find that, in addition to destabilizing the folded state, urea smooths the RNA free energy landscape by destabilizing specific configurations, and forming favorable interactions with RNA nucleobases. A linear concentration-dependence of the free energy (m-value) is observed, in agreement with the results of other RNA hairpins and proteins. Additionally, analysis of the hydrogen-bonding and stacking interactions within RNA primarily show temperature-dependence, while interactions between RNA and urea primarily show concentration-dependence. Lastly, our findings provide valuable insight into the effects of urea on RNA folding and describe the thermodynamics of a basic RNA hairpin as a function of solution chemistry.

Authors:
ORCiD logo [1]; ORCiD logo [1]
  1. Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Publication Date:
Research Org.:
Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Sponsoring Org.:
USDOE Laboratory Directed Research and Development (LDRD) Program
OSTI Identifier:
1358167
Report Number(s):
LA-UR-16-28139
Journal ID: ISSN 1520-6106
Grant/Contract Number:
AC52-06NA25396
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Journal of Physical Chemistry. B, Condensed Matter, Materials, Surfaces, Interfaces and Biophysical Chemistry
Additional Journal Information:
Journal Volume: 121; Journal Issue: 15; Journal ID: ISSN 1520-6106
Publisher:
American Chemical Society
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; Biological Science; RNA folding, molecular simulations, denaturants

Citation Formats

Miner, Jacob Carlson, and García, Angel Enrique. Equilibrium denaturation and preferential interactions of an RNA tetraloop with urea. United States: N. p., 2017. Web. doi:10.1021/acs.jpcb.6b10767.
Miner, Jacob Carlson, & García, Angel Enrique. Equilibrium denaturation and preferential interactions of an RNA tetraloop with urea. United States. doi:10.1021/acs.jpcb.6b10767.
Miner, Jacob Carlson, and García, Angel Enrique. Thu . "Equilibrium denaturation and preferential interactions of an RNA tetraloop with urea". United States. doi:10.1021/acs.jpcb.6b10767. https://www.osti.gov/servlets/purl/1358167.
@article{osti_1358167,
title = {Equilibrium denaturation and preferential interactions of an RNA tetraloop with urea},
author = {Miner, Jacob Carlson and García, Angel Enrique},
abstractNote = {Urea is an important organic cosolute with implications in maintaining osmotic stress in cells and differentially stabilizing ensembles of folded biomolecules. We report an equilibrium study of urea-induced denaturation of a hyperstable RNA tetraloop through unbiased replica exchange molecular dynamics. We find that, in addition to destabilizing the folded state, urea smooths the RNA free energy landscape by destabilizing specific configurations, and forming favorable interactions with RNA nucleobases. A linear concentration-dependence of the free energy (m-value) is observed, in agreement with the results of other RNA hairpins and proteins. Additionally, analysis of the hydrogen-bonding and stacking interactions within RNA primarily show temperature-dependence, while interactions between RNA and urea primarily show concentration-dependence. Lastly, our findings provide valuable insight into the effects of urea on RNA folding and describe the thermodynamics of a basic RNA hairpin as a function of solution chemistry.},
doi = {10.1021/acs.jpcb.6b10767},
journal = {Journal of Physical Chemistry. B, Condensed Matter, Materials, Surfaces, Interfaces and Biophysical Chemistry},
number = 15,
volume = 121,
place = {United States},
year = {Thu Feb 09 00:00:00 EST 2017},
month = {Thu Feb 09 00:00:00 EST 2017}
}

Journal Article:
Free Publicly Available Full Text
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Cited by: 2works
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  • The determination of reliable micelle aggregation numbers for ionic surfactants by means of equilibrium ultracentrifugation requires a correction for the preferential interactions which occur in multicomponent charged systems. Isopiestic distillation experiments on solutions containing the volatile solvent and the nonvolatile supporting electrolyte and varying amounts of the ionic surfactant lead directly to the desired correction for preferential interactions. Results for the surfactant, sodiumn dodecyl sulfate (SDDS), in various NaCl(aq) background solutions show that a substantial correction, increasing with increasing NaCl concentration, is required. Results on the surfactant, sodium decylsulfonate (SDS), show a smilar correction above the critical micelle concentration (cmc).more » Data for SDS below the cmc show a much different trend from that above, a condition not evident with SDDS because of the much lower cmc. If the interaction is interpreted as arising strictly from micelle charge, values for the micelle charge can be obtained. Sedimentation equilibrium experiments on SDDS in NaCl(aq) solutions gave aggregation numbers in good agreement with published values though generally higher. These higher results are consistent with the more reliable corrections for charge effects or preferential interactions available from the isopiestic distillation experiments. The aggregation numbers for SDDS increased with increasing NaCl concentration, consistent with published results. Precision density measurements, using a magnetic float densimeter having a precision of 1 ppM, were used to obtain accurate values for the partial specific volumes (anti ..nu..) of SDDS in NaCl(aq) and water for use in the ultracentrifuge calculations. The results show a slight increase in anti ..nu.. with NaCl concentration. Values for the cmc obtained from the density measurements are in excellent agreement with published values. 3 figures, 2 tables.« less
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