Musselman Catherine, Al-Hashimi Hashim M, Andricioaei Ioan
Department of Chemistry and The Center for Computational Medicine and Biology, University of Michigan, Ann Arbor, Michigan, USA.
Biophys J. 2007 Jul 15;93(2):411-22. doi: 10.1529/biophysj.107.104620. Epub 2007 Apr 20.
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.
HIV-1反式激活应答RNA元件（TAR）对病毒的生命周期至关重要。基于核磁共振（NMR）和流体动力学测量结果，有人提出TAR会经历大量的、集体的结构动力学变化，这些变化对其功能很重要。为了处理TAR中预期存在的整体扩散旋转与内部运动之间的显著耦合，我们在此利用模拟分子轨迹的各向同性重取向本征模动力学分析，以获得TAR动力学的详细描述以及精确量化的动力学关联模式。分析表明内部运动模式和整体运动模式不可分割，证实了集体结构域动力学的存在并揭示了其本质，此外还揭示这些运动的铰链集中在U23、C24和C41残基上。结果还表明RNA的环与核心之间以及环与凸起之间存在长程通信。此外，各向同性重取向本征模动力学分析从动力学角度解释了一些现有的生化突变研究，并为未来的结构动力学研究提出了新的突变。
