Applications of Field-Cycling NMR to Studies of Biomolecules.

描述（由申请人提供）：我们希望继续进行合作生物学研究，以证明和利用我们的场循环装置用于共享商业仪器的能力。我们的气动装置相对简单，旨在用于各种商用仪器，最终可能以某种商业形式或作为复制品用于许多其他实验室。广泛使用的商业仪器被设计为在某个固定场工作，例如，样品的质子自旋在500或600 MHz的频率下共振。我们的新设备允许研究人员对这些实验进行编程，以便样本在较低的磁场中度过关键的时间，几乎可以达到地球磁场。从这种能力，我们得到了一个更好的想法的时间尺度和振幅的随机运动在这些分子比否则无法获得实验。在某些情况下，这些运动是其生物活动的关键，而在其他情况下，它们可能会调节这些活动。我们的研究结果可以用来帮助理解酶的生化活性，或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动及其在结构中的位置。到目前为止，它已经适用于各种各样的分子，包括短的DMA双链体，酶和膜中的几种磷脂。我们的计划包括一个主要的继续工作（与玛丽罗伯茨教授，波士顿学院）的膜和他们如何与磷脂酶相互作用;和几个项目涉及其他合作者，对其他几种酶。我们将获得新的信息，在这些系统中的物理安排，特别是关于小分子（底物和抑制剂）弱结合酶的动力学。

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.