Computational Analysis of the Ribonuclease A Catalyzed Phosphate Ester Hydrolysis Mechanism using an Ab Initio Quantum-Based Model

使用基于量子的从头计算模型计算分析核糖核酸酶 A 催化的磷酸酯水解机制

• 批准号: 9983321
• 负责人: Brian Wladkowski
• 金额: $ 14.46万
• 依托单位: McDaniel College
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-03-15 至 2004-02-29
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9983321&HistoricalAwards=false
• 关键词: Computational; Analysis; Ribonuclease; Catalyzed; Phosphate

Brian Wladkowski of Western Maryland College, an RUI institution, is supported by the Theoretical and Computational Chemistry Program and the Molecular Biophysics Program to explore enzyme-catalyzed reaction mechanisms using ab initio quantum chemical approaches. The first goal of this research is to develop a comprehensive picture of the complete microscopic mechanism by which RNase functions to catalyze the hydrolysis of phosphodiesters. The second goal is to develop, through comparison with available kinetic and structural data on RNase A, a generalized methodology for characterizing other enzyme mechanisms using this approach. Once established, other related enzyme systems can be probed to make a priori quantitative predictions regarding site mutations.Characterization of the microscopic mechanisms by which enzymes carry out their designed catalytic role is a central focus in modern enzymology. Obtaining such detailed information is critical in predicting the behavior of enzymes and is essential for the design of new enzymes or modification of existing enzymes for specific catalytic tasks. In recent times, computational techniques have played an increasingly important role in this endeavor.

RUI机构西方马里兰州学院的Brian Wladkowski得到了理论和计算化学项目以及分子生物物理项目的支持，使用从头算量子化学方法探索酶催化反应机制。 本研究的第一个目标是全面了解RNase催化磷酸二酯水解的完整微观机制。 第二个目标是开发，通过与现有的动力学和结构数据的比较RNase A，一个通用的方法来表征其他酶的机制，使用这种方法。 一旦建立，其他相关的酶系统可以进行探测，使先验定量预测有关的网站mutations.Characterization的酶进行其设计的催化作用的微观机制是在现代酶学的中心焦点。 获得这些详细的信息对于预测酶的行为至关重要，对于设计新的酶或修饰现有的酶以完成特定的催化任务至关重要。 近年来，计算技术在这方面发挥了越来越重要的作用。