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谱（MRD）。MRD包含了从核磁共振实验中获得的大多数动态信息，因为它在很宽的范围内将谱功率密度映射为拉莫尔频率的函数。谱密度报告了调节磁耦合的分子内和分子间运动。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相关，利用磁铁对并在极化/检测场和可变演化场之间气动移动样品。有限的样品传输时间限制了可以测量的弛豫速率，使得测量大分子中的非稳定自旋变得困难，因为大的低场速率在通过低场区域的传输过程中破坏了磁化。我们使用交换稀释法解决了这个问题，该方法采用了一个热力学稳定的金属位点，观察到的配体与之快速交换。与电子磁矩结合的抗磁性金属位点可以定义一个独特的矢量，我们在10 ms到0.5 ps的时间范围内绘制其波动。我们建议将该技术应用于可溶性蛋白，膜结合蛋白和基于半胱氨酸双突变体的自旋对定位的小分子系统的分子动力学研究。我们建议：研究膜结合通道蛋白附近小分子的局部翻译扩散常数；最初利用广泛的突变文库来表征通道蛋白MscL中特定载体的波动；利用相当多的突变体文库来表征可溶性蛋白T4溶菌酶的波动，表征半固体或膜结合蛋白系统中四极核自旋分子的局部动力学和排序。我们建议开发一种可用于商用核磁共振光谱仪的条纹场探针。我们提出了新理论的实验测试，该理论很好地解释了动态非均质材料（如组织）中自旋晶格速率常数的磁场依赖性，并检查了这些系统中金属离子的电子弛豫特性，以了解MRI中造影剂靶向旋转不稳定位点的影响。

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.