Applications of Field-Cycling NMR to Studies of Biomolecules.

描述(由申请人提供)：我们希望继续合作生物学研究，展示并利用我们的野外循环装置的能力，用于共享的商业仪器。我们的气动装置相对简单，旨在用于各种商业仪器，也许最终会在许多其他实验室以商业形式或仿制品的形式使用。广泛使用的商业仪器被设计成在某些固定的磁场下工作，例如，样品的质子自旋以500或600 MHz的频率共振。我们的新设备允许研究人员对这些实验进行编程，以便样品在较低的磁场中度过关键时间，直到几乎地球的磁场。通过这种能力，我们对这些分子中随机运动的时间尺度和幅度有了更好的了解，而不是通过实验获得的。在某些情况下，这些运动是它们生物活性的关键，而在另一些情况下，它们可能会调节这些活动。然后，我们的结果可以用来帮助理解酶的生化活性，或者帮助验证它们的动力学的计算机模拟。我们的设备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，也可能对药物的开发有用。到目前为止，它已经适用于各种各样的分子，包括一个短的DMA双链，一个酶，以及几种膜上的磷脂。我们的计划包括(与波士顿学院玛丽·罗伯茨教授)在膜及其如何与磷脂酶相互作用方面的主要继续工作；以及涉及其他合作者的几个项目，涉及其他几种酶。我们将获得有关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。

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.