The Study of Isotropic and Anisotropic Motions in Proteins involving 13CO and 15ND

9513355 Zuiderweg博士将开发新的核磁共振波谱方法，通过测量13C/15N标记蛋白质的13CO和15ND松弛来研究生物大分子的动力学。这些实验将产生关于蛋白质骨架和含氮侧链的动力学信息，补充从通常进行的15NH核磁共振弛豫实验中获得的信息。将努力推广上述方法，以允许检测松弛机制之间是否存在相互关联。这样的测量将有助于发展蛋白质动力学现象的模型。用新的二维和三维核磁共振方法确定了异核松弛机制之间的相互关联(干涉)。这些方法主要是用蛋白质T4-溶菌酶(19 KDa)和结合酶(12 KDa)开发的，并使用蛋白质Hsc70上的一个肽环。初步数据表明，在T4-溶菌酶的骨架上，松弛互相关的程度是不均匀的，这表明这样测量的动力学特性是不均匀的，因此具有很高的信息含量。这些方法将被扩展到使用Hsc70蛋白来确定蛋白质表面环中松弛矢量之间的运动相关性的程度。这些方法将非常适合于区分不相交的链运动和只涉及几个铰点的协调运动。这些信息对于理解那些参与分子间相互作用的环和多肽的作用应该是重要的。这项研究旨在开发新的核磁共振波谱方法，用于研究生物大分子的动力学。这些方法将集中于羰基部分的核磁共振松弛行为，并将产生关于蛋白质骨架动力学的信息，补充从通常进行的侧重于酰胺部分的核磁共振松弛实验获得的信息。这些方法将主要用蛋白质T4-溶菌酶和结合酶来开发，并将扩展到确定蛋白质表面环中松弛载体之间的运动相关程度。这些信息对于理解参与分子间相互作用的环和肽的动力学特性应该是重要的。***

9513355 Zuiderweg Dr. Zuiderweg will develop new NMR spectroscopy methodologies for the study of dynamics in biological macromolecules by measuring 13 CO and 15ND relaxation in 13C/15N labeled proteins. These experiments will yield information on the dynamics of the protein backbone and nitrogen-containing sidechains, complementary to the information obtained from the commonly performed 15NH NMR relaxation experiments. Efforts will go into extending above methods to allow the detection of the presence or absence of cross correlation between relaxation mechanisms. Such measurements will help the development of models for dynamical phenomena in proteins. The cross correlation (interference) between the heteronuclear relaxation mechanisms is determined with new two- and three-dimensional NMR methods. The methods will be mostly developed with the proteins T4-lysozyme (19 kDa) and Binase (12 kDa), and using a peptide loop on the protein Hsc70. Preliminary data shows that the extent of relaxation cross correlation is non-uniform over the backbone of T4-lysozyme, indicating that the dynamical characteristics measured as such are non-uniform and therefore of high informational content. The methods will be extended for determining the extent of motional correlation between relaxation vectors in protein surface loops, using the Hsc70 protein. These methods will be well-suited to distinguish between disjointed-chain motions and concerted motions involving only a few hinge-points. This information should be of importance for the understanding of the role of those loops and peptides that are involved in intermolecular interactions. %%% The research is aimed at developing new nuclear magnetic resonance (NMR) spectroscopy methodologies for the study of dynamics in biological macromolecules. The methods will concentrate on the NMR relaxation behavior of carbonyl moieties and will yield information on the dynamics of the protein backbone, complementary to the information obtained from the commonly performed NMR relaxation experiments focusing on amide moieties. The methods will be mostly developed with the proteins T4-lysozyme and Binase and will be extended for determining the extent of motional correlation between relaxation vectors in protein surface loops. This information should be of importance for the understanding of the dynamical characteristics of loops and peptides that are involved in intermolecular interactions. ***