title: Free-energy landscape of a hyperstable RNA tetraloop.
abstract: 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.
authors.affiliation: Center for Nonlinear Studies, Los Alamos National Laboratory, Los Alamos, NM 87545; Department of Biological Sciences, Rensselaer Polytechnic Institute, Troy, NY 12180;
authors.forename: Jacob C
authors.initials: JC
authors.lastname: Miner
authors.affiliation: Department of Chemistry, University at Albany, State University of New York, Albany, NY 12222;
authors.forename: Alan A
authors.initials: AA
authors.lastname: Chen
authors.affiliation: Center for Nonlinear Studies, Los Alamos National Laboratory, Los Alamos, NM 87545; Department of Physics, Applied Physics, and Astronomy, Rensselaer Polytechnic Institute, Troy, NY 12180 agarcia@lanl.gov.
authors.forename: Angel E
authors.initials: AE
authors.lastname: García
mesh_terms: D056004:Molecular Dynamics Simulation; D012313:RNA / Q000737:chemistry*; D059370:RNA Folding; D020871:RNA Stability
chemical_list: D012313:RNA
keywords: RNA; free-energy landscape; molecular dynamics; pressure; tetraloop