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Title: Free-energy landscape of a hyperstable RNA tetraloop

Abstract

In this paper, we report the characterization of the energy landscape and the folding/unfolding thermodynamics of a hyperstable RNA tetraloop obtained through high-performance molecular dynamics simulations at microsecond timescales. Sampling of the configurational landscape is conducted using temperature replica exchange molecular dynamics over three isochores at high, ambient, and negative pressures to determine the thermodynamic stability and the free-energy landscape of the tetraloop. The simulations reveal reversible folding/unfolding transitions of the tetraloop into the canonical A-RNA conformation and the presence of two alternative configurations, including a left-handed Z-RNA conformation and a compact purine Triplet. Increasing hydrostatic pressure shows a stabilizing effect on the A-RNA conformation and a destabilization of the left-handed Z-RNA. Finally, our results provide a comprehensive description of the folded free-energy landscape of a hyperstable RNA tetraloop and highlight the significant advances of all-atom molecular dynamics in describing the unbiased folding of a simple RNA secondary structure motif.

Authors:
 [1];  [2];  [3]
  1. Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Rensselaer Polytechnic Inst., Troy, NY (United States). Dept. of Biological Sciences
  2. Univ. at Albany, Albany, NY (United States). Dept. of Chemistry
  3. Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Rensselaer Polytechnic Inst., Troy, NY (United States). Dept. of Physics, Applied Physics, and Astronomy
Publication Date:
Research Org.:
Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Sponsoring Org.:
USDOE; LANL Laboratory Directed Research and Development (LDRD) Program; National Science Foundation (NSF); National Inst. of Health (NIH) (United States)
OSTI Identifier:
1457303
Report Number(s):
LA-UR-15-28937
Journal ID: ISSN 0027-8424
Grant/Contract Number:  
AC52-06NA25396; MCB-137078; MCB-1050906; 5T32GM067545-08/9
Resource Type:
Accepted Manuscript
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Volume: 113; Journal Issue: 24; Journal ID: ISSN 0027-8424
Publisher:
National Academy of Sciences, Washington, DC (United States)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 74 ATOMIC AND MOLECULAR PHYSICS; Biological Science

Citation Formats

Miner, Jacob C., Chen, Alan A., and Garcia, Angel E. Free-energy landscape of a hyperstable RNA tetraloop. United States: N. p., 2016. Web. doi:10.1073/pnas.1603154113.
Miner, Jacob C., Chen, Alan A., & Garcia, Angel E. Free-energy landscape of a hyperstable RNA tetraloop. United States. doi:https://doi.org/10.1073/pnas.1603154113
Miner, Jacob C., Chen, Alan A., and Garcia, Angel E. Fri . "Free-energy landscape of a hyperstable RNA tetraloop". United States. doi:https://doi.org/10.1073/pnas.1603154113. https://www.osti.gov/servlets/purl/1457303.
@article{osti_1457303,
title = {Free-energy landscape of a hyperstable RNA tetraloop},
author = {Miner, Jacob C. and Chen, Alan A. and Garcia, Angel E.},
abstractNote = {In this paper, we report the characterization of the energy landscape and the folding/unfolding thermodynamics of a hyperstable RNA tetraloop obtained through high-performance molecular dynamics simulations at microsecond timescales. Sampling of the configurational landscape is conducted using temperature replica exchange molecular dynamics over three isochores at high, ambient, and negative pressures to determine the thermodynamic stability and the free-energy landscape of the tetraloop. The simulations reveal reversible folding/unfolding transitions of the tetraloop into the canonical A-RNA conformation and the presence of two alternative configurations, including a left-handed Z-RNA conformation and a compact purine Triplet. Increasing hydrostatic pressure shows a stabilizing effect on the A-RNA conformation and a destabilization of the left-handed Z-RNA. Finally, our results provide a comprehensive description of the folded free-energy landscape of a hyperstable RNA tetraloop and highlight the significant advances of all-atom molecular dynamics in describing the unbiased folding of a simple RNA secondary structure motif.},
doi = {10.1073/pnas.1603154113},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 24,
volume = 113,
place = {United States},
year = {2016},
month = {5}
}

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Cited by: 25 works
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