Magnetic Relaxation Dispersion

描述（由申请人提供）：核自旋-晶格弛豫速率常数的磁场依赖性提供了磁弛豫色散曲线（MRD）。MRD包含了大部分的动态信息，可从核磁共振实验，因为它映射频谱功率密度作为拉莫尔频率的函数在非常宽的范围内。谱密度报告内和分子间的运动，调制磁耦合。我们已经构建了MRD光谱仪，克服了低灵敏度和低分辨率通常与电流开关仪器，通过利用磁铁对和连续移动样品之间的偏振/检测场和可变演化场。有限的样品渡越时间限制了可以测量的弛豫速率，使得难以测量大分子中的非不稳定自旋，因为大的低场速率在通过低场区域的渡越期间破坏磁化。我们解决了这个问题，使用交换稀释方法，采用一个化学稳定的金属网站，所观察到的配体交换迅速。抗磁性金属网站结合电子磁矩可以定义一个独特的矢量的波动，我们映射的时间范围从10毫秒到0.5 ps。我们建议将这种技术应用于可溶性蛋白质，膜结合蛋白质和小分子系统的分子动力学研究，利用基于半胱氨酸双突变体的自旋对的本地化。我们建议：检测膜结合通道蛋白附近的小分子的局部翻译扩散常数;表征通道蛋白MscL中特定载体的波动，最初利用广泛的突变体文库;为了利用大量的突变体文库表征可溶性蛋白T4溶菌酶内的波动，描述半固体或膜结合蛋白质系统中四极核自旋轴承分子的局部动力学和有序性。我们建议开发一种边缘场探针，可用于商业NMR光谱仪。我们提出了新的理论，以及占磁场的依赖性的自旋-晶格速率常数在动态异质材料，如组织和检查在这些系统中的金属离子的电子弛豫特性的实验测试，以了解磁共振成像中的靶向造影剂旋转nonlabile网站的影响。

DESCRIPTION (provided by applicant): The magnetic field dependence of the nuclear spin-lattice relaxation rate constant provides the Magnetic Relaxation Dispersion profile (MRD). The MRD contains most of the dynamical information that is available from a nuclear magnetic resonance experiment because it maps spectral power densities as a function of Larmor frequency over very wide ranges. The spectral densities report intra and intermolecular motions that modulate magnetic couplings. We have constructed MRD spectrometers that overcome the low sensitivity and low resolution usually associated with current switched instruments by utilizing a magnet pair and pneumatically moving a sample between a polarization/detection field and a variable evolution field. The finite sample transit time limits the relaxation rates that may be measured making it difficult to measure nonlabile spins in macromolecules because the large low-field rates destroy magnetization during transit through low field regions. We solve this problem using an exchange dilution method employing a thermodynamically stable metal site with which an observed ligand exchanges rapidly. The diamagnetic metal site in combination with an electron magnetic moment may define a unique vector the fluctuations of which we map over the time range from 10 ms to 0.5 ps. We propose to apply this technology to the study of molecular dynamics in soluble proteins, membrane-bound proteins, and small molecule systems utilizing localization of spin pairs based on cysteine double mutants. We propose: to examine localized translational diffusion constants for small molecules in the immediate vicinity of membrane bound channel proteins; to characterize fluctuations of specific vectors in channel protein MscL initially utilizing an extensive mutant library; to characterize fluctuations within the soluble protein T4 lysozyme utilizing a considerable mutant library, to characterize the local dynamics and ordering of quadrupolar nuclear spin bearing molecules in semisolid or membrane-bound protein systems. We propose to develop a fringe-field probe that may be utilized in commercial NMR spectrometers. We propose experimental tests of the new theory that accounts well for the magnetic field dependence of spin-lattice rate constants in dynamically heterogeneous materials like tissues and examine the electron relaxation properties of metal ions in these systems to understand effects of targeting contrast agents in MRI to rotationally nonlabile sites.