期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 113, 期 24, 页码 6665-6670出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1603154113
关键词
RNA; free-energy landscape; molecular dynamics; tetraloop; pressure
资金
- National Science Foundation (NSF) [MCB-137078, MCB-1050906]
- NIH Biotechnology Training Grant [5T32GM067545-08/9]
- US DOE LDRD funds
- Direct For Biological Sciences
- Div Of Molecular and Cellular Bioscience [1050966] Funding Source: National Science Foundation
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.
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