Applications of Field-Cycling NMR to Studies of Biomolecules.

场循环核磁共振在生物分子研究中的应用。

• 批准号: 6963056
• 负责人: ALFRED Guillou REDFIELD
• 金额: $ 15.4万
• 依托单位: BRANDEIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-23 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6963056
• 关键词: biomedical equipment resource; chemical kinetics; conformation; enzyme activity; membrane structure; nuclear magnetic resonance spectroscopy; protein binding; protein protein interaction; structural biology

DESCRIPTION (provided by applicant): We wish to continue collaborative biological research demonstrating and utilizing the capabilities of our field-cycling device for use in shared commercial instruments. Our pneumatic device is relatively simple and is intended to be used in a variety of commercially available instruments, perhaps eventually at many other laboratories in some commercial form or as copies. Widely used commercial instruments are designed to work at some fixed field, where, for example, the sample's proton spins resonate at frequencies such as 500, or 600 MHz. Our new device allows researchers to program these experiments so that samples spend key parts of the time in lower fields, down to almost the earth's magnetic field. From this capability we get a better idea about time-scales and amplitudes of random-seeming motions in these molecules than cannot otherwise be obtained experimentally. In some cases these motions are key to their biological activity, while in others they may regulate these activities. Our results can then be used to help understand biochemical activity of enzymes, or to help validate computer simulations of their dynamics. Our device may also be useful for development of drugs, by helping to locate unknown activities in proteins, and their location in the structure. It has been applicable to a wide variety of molecules so far, including a short DMA duplex, an enzyme, and several phospholipids in membranes. Our plans include a major continuation of work (with Prof. Mary Roberts, Boston College) on membranes and how they interact with phospholipases; and several projects involving other collaborators, on several other enzymes. We will obtain new information about physical arrangements in these systems, and especially about dynamics of small molecules (substrates and inhibitors) weakly bound to enzymes.

描述（由申请人提供）：我们希望继续合作生物研究，展示和利用我们的现场循环设备的能力，用于共享的商业仪器。我们的气动装置相对简单，旨在用于各种商用仪器，也许最终在许多其他实验室以某种商业形式或作为副本。广泛使用的商业仪器被设计成在一些固定的场中工作，例如，样品的质子自旋在500或600兆赫兹的频率上共振。我们的新设备允许研究人员对这些实验进行编程，这样样本就可以在低磁场中度过关键的时间，低到几乎相当于地球的磁场。从这种能力中，我们可以更好地了解这些分子中看似随机的运动的时间尺度和幅度，而不是通过实验获得的。在某些情况下，这些运动是其生物活性的关键，而在其他情况下，它们可能调节这些活动。我们的结果可以用来帮助理解酶的生化活性，或者帮助验证其动力学的计算机模拟。我们的设备也可以用于药物的开发，通过帮助定位蛋白质中的未知活性，以及它们在结构中的位置。到目前为止，它已经适用于各种各样的分子，包括短的DMA双工，酶和膜中的几种磷脂。我们的计划包括（与波士顿学院的Mary Roberts教授）继续研究膜及其如何与磷脂酶相互作用；还有其他合作者参与的几个项目，研究其他几种酶。我们将获得关于这些系统中物理排列的新信息，特别是关于与酶弱结合的小分子（底物和抑制剂）的动力学。