Free-energy landscape of a hyperstable RNA tetraloop

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...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2016-06, Vol.113 (24), p.6665-6670
Main Authors: Miner, Jacob C., Chen, Alan A., García, Angel E.
Format: Article
Language:English
Subjects:
ATOMIC AND MOLECULAR PHYSICS
BASIC BIOLOGICAL SCIENCES
Biological Science
Biological Sciences
Molecular Dynamics Simulation
Ribonucleic acid
RNA
RNA - chemistry
RNA Folding
RNA Stability
Sampling
Simulation
Temperature
Thermodynamics
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Summary: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. 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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1603154113