What NMR Relaxation Can Tell Us about the Internal Motion of an RNA Hairpin:  A Molecular Dynamics Simulation Study

Classical molecular dynamics simulations of a 14-mer UUCG RNA hairpin are performed to study its conformational dynamics and corresponding NMR relaxation parameters. The direct calculation of the relaxation rates from the trajectory yields good agreement with experiment, indicating the validity of the theoretical model. Various ways to provide a link between theory and experiment are considered, including the "model-free approach" of Lipari and Szabo and Gaussian axial fluctuation model of Brüschweilwer. It is studied if the underlying assumptions of these approaches are satisfied in the case of a flexible RNA hairpin. Being consistent with the analysis of the NMR experiments, Lipari-Szabo fits of the first 100 or 1000 ps of the internal correlation functions lead to a nice agreement between calculated and experimental order parameters and internal correlation times. Finally, the relation between NMR order parameters and the underlying internal motion of the RNA hairpin is discussed in detail. A principal component analysis reveals that the principal motions of the molecule account only partially for the measured NMR order parameters, because the latter are insensitive to internal dynamics occurring on a nanosecond time scale due to molecular tumbling.