Protein dynamics studies by hydrogen exchange

通过氢交换进行蛋白质动力学研究

• 批准号: 7492956
• 负责人: S. Walter ENGLANDER
• 金额: $ 23.25万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7492956
• 关键词: Active Sites; Behavior; Characteristics; Collaborations; Condition; DNA Sequence Rearrangement; Data; Development; Dihydrofolate Reductase; Dill; Dimensions; Electrostatics; Enzymatic Biochemistry; Equilibrium; Hydrogen; Kinetics; Measurement; Measures; Methodology; Methods; Micrococcal Nuclease; Modeling; Motion; Mutation; Numbers; Play; Probability; Property; Protein Dynamics; Proteins; Rate; Reaction; Research Personnel; Role; Running; Site; Testing; Theoretical model; Titrations; Work; cytochrome c; design; experience; improved; insight; member; numb protein; pressure; programs; protein folding; protein function; protein structure; research study; response

DESCRIPTION (provided by applicant): Hydrogen exchange measurements have been able, in some cases, to distinguish different kinds of protein motions and to provide site-resolved information on their identity, their extent, their equilibrium and kinetic parameters, their response to ambient conditions and mutations, and their relationship to functional properties. As part of the effort to understand the significance of the dynamic dimension of protein structure and its role in protein function, these hydrogen exchange capabilities need to be improved and extended to more proteins. Studies are proposed of staphylococcal nuclease, dihydrofolate reductase, and cytochrome c initially, and other proteins more broadly. To better understand the relationships that connect hydrogen exchange behavior to protein structure and dynamics, a large quantity of results will be used to test and refine theoretical models that attempt to relate protein properties and hydrogen exchange. To extend the scope of native state hydrogen exchange methods, the mode of action of osmolytes, and their use as reverse denaturants, will be pursued. Also, larger proteins, which promise to change the balance between local fluctuations and larger unfolding reactions measured by hydrogen exchange, will be studied. To study the functional role of the dynamic dimension of protein structure, hydrogen exchange approaches will be applied to the study of enzymatic function.

描述（由申请人提供）：在某些情况下，氢交换测量能够区分不同种类的蛋白质运动，并提供有关其身份、程度、平衡和动力学参数、对环境条件的响应的位点解析信息和突变，以及它们与功能特性的关系。作为理解蛋白质结构动态维度的重要性及其在蛋白质功能中的作用的努力的一部分，这些氢交换能力需要改进并扩展到更多的蛋白质。最初建议对葡萄球菌核酸酶、二氢叶酸还原酶和细胞色素 c 以及更广泛的其他蛋白质进行研究。为了更好地理解氢交换行为与蛋白质结构和动力学之间的关系，将使用大量结果来测试和完善试图将蛋白质特性和氢交换联系起来的理论模型。为了扩大天然状态氢交换方法的范围，将研究渗透剂的作用模式及其作为反向变性剂的用途。 此外，还将研究较大的蛋白质，它们有望改变局部波动和通过氢交换测量的较大展开反应之间的平衡。为了研究蛋白质结构动态维度的功能作用，氢交换方法将应用于酶功能的研究。