Magnetic Relaxation Dispersion

磁弛豫色散

• 批准号: 7065606
• 负责人: Robert George Bryant
• 金额: $ 24.4万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-06-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7065606
• 关键词: DNA; calmodulin; chemical structure function; diffusion; electrolytes; lysozyme; magnetic field; membrane activity; membrane channels; membrane proteins; molecular dynamics; molecular probes; nuclear magnetic resonance spectroscopy; polymers; relaxation spectrometry; small molecule; surface property; technology /technique development; time resolved data

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.

描述(申请人提供)：核自旋-晶格驰豫速率常数与磁场的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动力学信息，因为它在非常大的范围内将光谱功率密度作为Larmor频率的函数进行映射。光谱密度报告了调制磁耦合的分子内和分子间运动。我们已经构建了MRD光谱仪，通过利用磁体对并在极化/检测场和可变演化场之间气动移动样品，克服了通常与当前开关仪器相关的低灵敏度和低分辨率。有限的样品渡越时间限制了可以测量的驰豫速率，这使得测量大分子中不稳定的自旋变得困难，因为大的低场速率在穿过低场区域时破坏了磁化。我们使用交换稀释法解决了这个问题，该方法使用了热力学上稳定的金属位置，观察到的配体与该位置快速交换。反磁金属位置与电子磁矩相结合可以定义一个独特的矢量，我们可以在从10ms到0.5ps的时间范围内映射它的涨落。我们建议将这项技术应用于利用基于半胱氨酸双突变体的自旋对定位来研究可溶性蛋白质、膜结合蛋白质和小分子系统的分子动力学。我们建议：研究膜结合蛋白附近小分子的局部平移扩散常数；最初利用一个广泛的突变体文库来表征通道蛋白MSCL中特定载体的波动；利用相当大的突变文库来表征可溶性蛋白T4溶菌酶中的波动，以表征半固体或膜结合蛋白体系中四极核自旋承载分子的局部动力学和有序性。我们建议开发一种可用于商业核磁共振光谱仪的条纹场探头。我们提出了对新理论的实验测试，该理论很好地解释了组织等动态非均质材料中自旋-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，以了解磁共振成像中靶向对比剂对旋转不稳定位置的影响。