iRED Analysis of TAR RNA Reveals Motional Coupling, Long-Range Correlations, and a Dynamical Hinge

The HIV-1 transactivation response RNA element (TAR), which is essential to the lifecycle of the virus, has been suggested, based on NMR and hydrodynamic measurements, to undergo substantial, collective, structural dynamics that are important for its function. To deal with the significant coupling between overall diffusional rotation and internal motion expected to exist in TAR, here we utilize an isotropic reorientational eigenmode dynamics analysis of simulated molecular trajectories to obtain a detailed description of TAR dynamics and an accurately quantified pattern of dynamical correlations. The analysis demonstrates the inseparability of internal and overall motional modes, confirms the existence and reveals the nature of collective domain dynamics, and additionally reveals that the hinge for these motions is centered on residues U23, C24, and C41. Results also indicate the existence of long-range communication between the loop and the core of the RNA, and between the loop and the bulge. Additionally, the isotropic reorientational eigenmode dynamics analysis explains, from a dynamical perspective, several existing biochemical mutational studies and suggests new mutations for future structural dynamics studies.