Dynamic Properties that Enhance Enzyme Function

描述（由申请人提供）：本研究的长期目标包括开发方法，以允许蛋白质结构的折叠，灵活性和动力学被询问，以及以新的方式开发和使用荧光探针，以增强我们对蛋白质结构，动力学和功能的理解。在拟议的五年研究期间，工作重点将是通过稳态、预稳态和单分子动力学研究来研究修饰的DHFR的机制。荧光光谱将用于研究蛋白质构象变化及其与DHFR催化关键步骤的关系。 公共卫生相关性：本项目的目的是描述和量化的特定序列，结构和动力学特性，操作，以提高酶催化。拟议的研究将为酶功能提供重要的见解，并将促进蛋白质设计和药物发现工作。酶DHFR，这是重要的抗菌药物和抗微生物药物的目标，将是我们努力的重点。

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.