Structure and Dynamics of Proteins from NMR Orientational Data

建议继续探索一个潜在的来源，新的信息在溶液中的蛋白质结构和动力学。 新的信息来自于蛋白质NMR谱中的残余偶极耦合，当它们被诱导具有低水平的空间有序性时，它们与各向异性介质（如水性液晶）的相互作用，或者它们与足够高的磁场的直接相互作用。容易测量的耦合提供了一个有效的途径，通过其依赖于平均相互作用矢量的长度和方向的蛋白质结构和动力学的信息。 除了分离蛋白质的基本结构研究，目标包括：（i）开发和应用一种定义溶液中蛋白质-蛋白质相互作用的几何形状的方法，以及（ii）开发和应用一种量化蛋白质内部运动幅度的策略。 蛋白质-蛋白质相互作用的几何定义有助于将结构和机制描述从孤立的蛋白质结构域转移到理解完整生命过程所需的系统范围的描述。内部运动幅度的量化提供了对蛋白质功能的机械细节的深入了解，这些细节可能在结构的静态表示中被遗漏。 测试方法的目标系统包括一些良好的特征蛋白质，如肌红蛋白和rubredoxin，但也包括最近确定的电子转移合作伙伴的rubredoxin从嗜热organis.In一般的影响，该项目将提供培训机会，本科生，研究生和博士后学生。 在后基因组时代，在分子水平上定义蛋白质功能的方法的开发和使用方法的培训变得越来越重要。 大量的蛋白质序列信息可以对新的生物技术产品的开发和疾病的治疗产生影响，但前提是对蛋白质功能有足够的了解。

The continued exploration of a potential source of new information on protein structure and dynamics in solution is proposed. The new information comes from residual dipolar couplings seen in NMR spectra of proteins when they are induced to have low levels of spatial order by their interaction with an anisotropic medium, such as an aqueous liquid crystal, or by their direct interaction with a sufficiently high magnetic field. The easily measured couplings provide an efficient route to information about protein structure and dynamics through their dependence on average interaction vector length and orientation. In addition to basic structural studies of isolated proteins, objectives include, (i) the development and application of a method for defining the geometry of protein-protein interactions in solution, and (ii) the development and application of a strategy for quantifying the amplitudes of internal motions in proteins. The definition of the geometry of protein-protein interaction serves to move structural and mechanistic descriptions from isolated protein domains toward the system wide descriptions that are needed for understanding complete life processes. The quantification of amplitudes of internal motion provides insight into mechanistic details of protein function that might be missed in static representations of structure. The target systems for testing the methodology include a number of well characterized proteins such as myoglobin and rubredoxin, but also include recently identified electron transfer partners of a rubredoxin from a thermophilic organism.In terms of general impact, this project will provide training opportunities for undergraduate, graduate, and postdoctoral students. Development of methods and training in the use of methods that can define protein function at a molecular level is becoming increasingly important in a post-genomic era. Vast quantities of protein sequence information can have an impact on the development of new biotechnology products, and the treatment of disease, but only with an adequate understanding of protein function.