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，氢交换测量值已经能够区分不同种类的蛋白质运动，并提供有关其身份，其程度，平衡和动力学参数，对环境条件和突变的反应以及对功能特性的关系的现场分辨信息。作为了解蛋白质结构动态维度及其在蛋白质功能中的作用的重要性的一部分，这些氢交换能力需要提高并扩展到更多的蛋白质。最初提出了对葡萄球菌核酸酶，二氢叶酸还原酶和细胞色素C的研究，以及其他蛋白质的研究。为了更好地了解将氢交换行为与蛋白质结构和动态联系起来的关系，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的理论模型。为了扩展天然状态氢交换方法的范围，将追求渗透剂的作用方式及其用作反向变性剂。 同样，将研究较大的蛋白质，该蛋白质有望改变局部波动之间的平衡和通过氢交换测得的较大的发展反应。为了研究蛋白质结构动态维度的功能作用，将应用氢交换方法用于酶促功能的研究。