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

这项研究的目的是用核磁共振和计算方法研究蛋白质动力学。关于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。这些信息将通过在不同化学条件和不同磁场下对包括泛素和转录因子在内的统一标记蛋白质的核自旋自相关和交叉相关松弛测量来获得。数据的解释将集中在内部和整体的运动各向异性效应和相关的动力学。分析和半经验模型将从扩展分子动力学(MD)计算机模拟中得到。密度泛函理论(DFT)将被应用于MD快照的时间序列，以量子力学方法确定驰豫-活性自旋相互作用的强度和取向，这对核磁共振弛豫数据的解释是至关重要的。了解蛋白质动力学对于包括分子识别在内的许多生化事件是至关重要的。这项研究的总体目标是开发新的方法来真实、准确和可理解地描述复杂蛋白质在溶液中的动力学及其在生物相关系统中的应用。

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.