Anisotropic and Correlated Proteins Dynamics Characterized by a Combination of NMR Relaxation, MD Computer Simulations, and Density Functional Theory

本研究的目的是通过核磁共振和计算方法研究蛋白质动力学。动力学的详细信息对于在原子水平上理解蛋白质的功能是高度相关的。这些信息将从核自旋自旋和均匀标记的蛋白质的交叉相关弛豫测量中获得，包括泛素和转录因子在不同的化学条件和不同的磁场下。数据的解释将侧重于内部和整体运动各向异性效应和相关动力学。分析和半经验模型将从扩展分子动力学（MD）计算机模拟中导出。密度泛函理论（DFT）将应用于MD快照的时间序列，以量子力学的方式确定弛豫-活性自旋相互作用的强度和方向，这对核磁共振弛豫数据的解释至关重要。了解蛋白质动力学对包括分子识别在内的许多生化事件具有重要的基础意义。本研究的总体目标是开发新的方法，以实现对溶液中复杂蛋白质动力学的现实、准确和可理解的描述，并将其应用于生物学相关系统。

MCB 9904875BruschweilerThe objective of this research is to study protein dynamics by NMR and computational approaches. Detailed information on dynamics is highly relevant for understanding the function of proteins at an atomic level. Such information will be gained from nuclear spin auto-and cross-correlated relaxation measurements of uniformly labeled proteins, including ubiquitin and a transcription factor under various chemical conditions and at different magnetic fields. Interpretation of the data will focus on internal and overall motional anisotropy effects and correlated dynamics. Analytical and semi-empirical models will be derived from extended molecular dynamics (MD) computer simulations. Density functional theory (DFT) will be applied to time series of MD snapshots for the quantum-mechanical determination of the strengths and orientations of the relaxation-active spin interactions which are crucial for NMR relaxation data interpretation. Understanding protein dynamics is of fundamental importance for many biochemical events, including molecular recognition. The overall goal of this research is to develop new methods for a realistic, accurate, and yet comprehensible description of complex protein dynamics in solution and their application to biologically relevant systems.