CRYSTALLOGRAPHIC STRUCTURE ANALYSES OF PROTEIN/LIGAND COMPLEXES

蛋白质/配体复合物的晶体结构分析

• 批准号: 8170116
• 负责人: Ronald E Stenkamp
• 金额: $ 0.13万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8170116
• 关键词: Biotin; Complex; Computer Retrieval of Information on Scientific Projects Database; Data; Data Set; Drug Interactions; Environment; Funding; G-Protein-Coupled Receptors; GTP-Binding Proteins; Grant; Institution; Ligands; Molecular Structure; Protein Dynamics; Proteins; Research; Research Personnel; Resolution; Resources; Rhodopsin; Signal Transduction; Signaling Protein; Source; Streptavidin; Structure; Synchrotrons; United States National Institutes of Health; computerized data processing; molecular dynamics; mutant; small molecule; synchrotron radiation; ultra high resolution

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 该提案包括两个涉及蛋白质-配体相互作用研究的项目。 第一个是继续寻找视紫红质及其与其他信号蛋白复合物的有序晶体。 G蛋白偶联受体如何响应其环境并与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。 我们正试图结晶与信号过程相关的复合物，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。 如果没有同步辐射源，很难确定它们的反射效果如何。 我们的第二个项目涉及获得高或超高分辨率的衍射数据链霉亲和素突变体和它们的生物素复合物。 我们希望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？）交互. 我们目前有几个高分辨率的数据集进行比较，但我们预计将扩大我们的研究，包括更多的突变体。