MAGNETIC RELAXATION DISPERSION

核自旋-晶格弛豫速率的磁场依赖性提供了磁弛豫色散谱。MRD包含了从核磁共振实验中获得的大多数分子动力学信息，并为定义分子内和分子间运动提供了非常强大的高分辨率工具。我们构建了一种仪器，通过在高场极化和探测磁铁和卫星弛豫磁铁之间气动移动样品，解决了MRD实验中灵敏度和分辨率低的标准难题。通过改变弛豫磁体中的磁场，我们可以绘制磁流变图。我们在很大程度上解决了样品密封、穿梭时间和弛豫率窗口的问题。我们建议直接使用该光谱仪来映射谱密度函数来解决分子动力学问题，谱密度函数是表征瞬时距离和方向时间波动的自相关函数的傅里叶变换。可以研究的时间尺度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的冷凝或双层区域中的局部平移扩散常数。我们将测量其他感兴趣的溶质在膜表面的局部平移扩散常数。我们将测量与小分子结构波动相关的谱密度函数，并将其与数十ps时间范围内分子动力学模拟计算的谱密度函数进行比较。我们将进一步开发测量蛋白质内部动力学的方法，使用选择的自旋对，这些自旋对可能通过各向同性标记方法结合标准光谱编辑序列进行光谱分离。使用这种方法，我们期望定义蛋白质中重要的铰链运动频率，以及其他低频和高频动力学，如氨基酸侧链的关键活性位点运动。初期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。我们期望对这些动态的理解将极大地影响我们对功能的理解。

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.