MAGNETIC RELAXATION DISPERSION

核自旋-晶格弛豫速率与磁场的依赖关系提供了磁弛豫色散分布(MRD)。MRD包含了核磁共振实验中可用的大部分分子动力学信息，并为定义分子内和分子间运动提供了一个非常强大和高分辨率的工具。我们建造了一台仪器，通过在高场极化和探测磁铁与卫星弛豫磁铁之间气动移动样品，绕过了MRD实验中灵敏度和分辨率低的标准困难。通过改变弛豫磁体中的磁场，我们可以映射MRD。我们在很大程度上解决了样品容纳、穿梭时间和松弛速率窗口的问题。我们建议使用这台光谱仪直接处理分子动力学，以映射光谱密度函数，这是自相关函数的傅里叶变换，它表征了相互作用距离和取向的时间涨落。可以调查的时间范围从十分之一毫秒到十分之一皮秒。我们将测量离子在膜和线性聚电解质，特别是DNA的冷凝区或双层区的局域平移扩散常数。我们将测量其他感兴趣的溶质在膜表面的局域平移扩散常数。我们将测量与小分子结构涨落相关的光谱密度函数，并将它们与在数十ps的时间范围内通过分子动力学模拟计算的光谱密度函数进行比较。我们将进一步开发使用选定的自旋对来测量蛋白质内部动力学的方法，这些自旋对可以通过各向同性标记方法与标准光谱编辑序列相结合进行光谱分离。使用这种方法，我们希望定义蛋白质中重要的铰链运动频率以及其他低频率和高频动力学，例如氨基酸侧链的关键活性部位运动。最初的蛋白质实验将集中在钙调蛋白和T4溶菌酶上；然而，这些方法是通用的。我们预计，对这些动力学的理解将对我们对功能的理解产生重大影响。

The magnetic field dependence of the nuclear spin-lattice relaxation rate provides the Magnetic Relaxation Dispersion profile (MRD). The MRD contains most of the molecular dynamical information that is available from a nuclear magnetic resonance experiment, and offers a very powerful as well as high resolution tool for defining both intra and intermolecular motions. We have constructed an instrument that circumvents the standard difficulties of low sensitivity and resolution in MRD experiments by pneumatically moving a sample between a high field polarization and detection magnet and a satellite relaxation magnet. By varying the field in the relaxation magnet, we may map the MRD. We have largely solved the problems of sample containment, shuttle time, and relaxation rate windows. We propose to address molecular dynamics directly using this spectrometer to map spectral density functions, which are Fourier transforms of autocorrelation functions that characterize the time fluctuations of intermoment distances and orientations. The time scale that may be investigated ranges from tenths of milliseconds to tenths of picoseconds. We will measure localized translational diffusion constants for ions in condensation or double layer regions of membranes and linear polyelectrolytes, DNA in particular. We will measure localized translational diffusion constants for other solutes of interest at membrane surfaces. We will measure spectral density functions associated with small-molecule structural fluctuations and compare them with spectral density functions computed from molecular dynamics simulations in the time range of tens of ps. We will develop further the methods to measure internal dynamics in proteins using selected spin pairs that may be spectrally isolated by isotropic labeling methods combined with standard spectral editing sequences. Using this approach we expect to define important hinge motion frequencies in proteins as well as other low and high frequency dynamics such as crucial active site motions of amino acid side chains. Initial protein experiments will be focused on calmodulin and T4 lysozyme; however, the approaches are general. We expect that understanding these dynamics will impact our understanding of function significantly.