Referencing Strategy for the Direct Comparison of Nuclear Magnetic Resonance and Molecular Dynamics Motional Parameters in RNA

Nuclear magnetic resonance (NMR) spectroscopy and molecular dynamics (MD) simulations are both techniques that can be used to characterize the structural dynamics of biomolecules and their underlying time scales. Comparison of relaxation parameters obtained through each methodology allows for cross validation of techniques and for complementarity in the analysis of dynamics. Here we present a combined NMR/MD study of the dynamics of HIV-1 transactivation response (TAR) RNA. We compute relaxation constants (R-1, R-2, and NOE) and model-free parameters (S-2 and tau) from a 65 ns molecular dynamics (MD) trajectory and compare them with the respective parameters measured in a domain-elongation NMR experiment. Using the elongated domain as the frame of reference for all computed parameters allows for a direct comparison between experiment and simulation. We see good agreement for many parameters and gain further insight into the nature of the local and global dynamics of TAR, which are found to be quite complex, spanning multiple time scales. For the few cases where agreement is poor, comparison of the dynamical parameters provides insight into the limits of each technique. We suggest a frequency-matching procedure that yields an upper bound for the time scale of dynamics to which the NMR relaxation experiment is sensitive.