NMR and MD studies of the temperature-dependent dynamics of RNA YNMG-tetraloops

Institut für Organische Chemie und Chemische Biologie, Center for Biomolecular Magnetic Resonance, Frankfurt/M, Germany.
Nucleic Acids Research (Impact Factor: 9.11). 05/2008; 36(6):1928-40. DOI: 10.1093/nar/gkm1183
Source: PubMed


In a combined NMR/MD study, the temperature-dependent changes in the conformation of two members of the RNA YNMG-tetraloop
motif (cUUCGg and uCACGg) have been investigated at temperatures of 298, 317 and 325 K. The two members have considerable
different thermal stability and biological functions. In order to address these differences, the combined NMR/MD study was
performed. The large temperature range represents a challenge for both, NMR relaxation analysis (consistent choice of effective
bond length and CSA parameter) and all-atom MD simulation with explicit solvent (necessity to rescale the temperature). A
convincing agreement of experiment and theory is found. Employing a principle component analysis of the MD trajectories, the
conformational distribution of both hairpins at various temperatures is investigated. The ground state conformation and dynamics
of the two tetraloops are indeed found to be very similar. Furthermore, both systems are initially destabilized by a loss
of the stacking interactions between the first and the third nucleobase in the loop region. While the global fold is still
preserved, this initiation of unfolding is already observed at 317 K for the uCACGg hairpin but at a significantly higher
temperature for the cUUCGg hairpin.

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Available from: Jan Ferner
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