CRYSTALLOGRAPHIC STRUCTURE ANALYSES OF PROTEIN/LIGAND COMPLEXES

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 这项建议包括两个项目，涉及蛋白质-配体相互作用的研究。首先是继续寻找有序的视紫红质晶体及其与其他信号蛋白的复合体。G蛋白偶联受体如何对环境作出反应，并与G蛋白相互作用以产生细胞内信号，在分子结构水平上尚不清楚。我们正在尝试结晶与信号过程相关的复合体，并希望使用同步辐射来确定它们的结构。我们目前的晶体很小，而且排列不整齐。如果不能获得同步加速器源，很难确定它们的衍射率有多高。我们的第二个项目涉及获得链霉亲和素突变体及其生物素复合体的高或超高分辨率的衍射数据。我们想要比较分子动力学模拟和各向异性原子位移参数，以更好地了解蛋白质/小分子(药物？)的动力学。互动。我们目前有几个用于比较的高分辨率数据集，但我们预计将扩大我们的研究，以包括更多的突变。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This proposal covers two projects involving studies of protein-ligand interactions. The first is a continuing search for well-ordered crystals of rhodopsin and its complexes with other signaling proteins. How G protein-coupled receptors respond to their environment and interact with G proteins to create intracellular signals is not understood at the molecular structure level. We are attempting to crystallize complexes relevant to the signaling process and want to use synchrotron radiation to determine their structures. Our current crystals are small and poorly-ordered. How well they diffract would be difficult to determine without access to synchrotron sources. Our second project involves obtaining high or ultra-high resolution diffraction data for streptavidin mutants and their biotin complexes. We want to compare molecular dynamics simulations and anisotropic atomic displacement parameters to better understand the dynamics of protein/small molecule (drug?) interactions. We currently have several high-resolution data sets for the comparison, but we anticipate expanding our studies to include additional mutants.