Dynamic Properties that Enhance Enzyme Function

描述（由申请人提供）：本研究的长期目标包括发展研究蛋白质结构的折叠、灵活性和动力学的方法，以及开发和使用荧光探针的新方法，以增强我们对蛋白质结构、动力学和功能的理解。在拟建的5年研究期内，将重点通过稳态、预稳态和单分子动力学研究对改性DHFRs的机理进行研究。荧光光谱将用于研究蛋白质的构象变化及其与DHFR催化关键步骤的关系。

DESCRIPTION (provided by applicant): The long term goals of this research include the development of methodology to permit the folding, flexibility and dynamics of protein structure to be interrogated, and the development and use of fluorescent probes in novel ways to enhance our understanding of protein structure, dynamics and function. During the five years of proposed research, the focus of efforts will be on study of the mechanism of modified DHFRs through steady state, pre-steady state and single molecule kinetic studies. Fluorescence spectroscopy will be used to study the protein conformational changes and their association with the key steps in DHFR catalysis. PUBLIC HEALTH RELEVANCE: The present project is aimed at describing and quantifying the particular sequence, structural and dynamic properties that operate to enhance enzymatic catalysis. The proposed studies will provide important insights into enzyme function and will foster protein design and drug discovery efforts. The enzyme DHFR, which is the target of important antineoplastic and antimicrobial drugs, will be the focus of our efforts.