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

西马里兰学院的Brian Wladkowski，是一个RUI机构，由理论与计算化学项目和分子生物物理学项目支持，利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。第二个目标是通过与现有的RNase A的动力学和结构数据进行比较，开发一种通用的方法来描述使用这种方法的其他酶机制。一旦建立，其他相关的酶系统可以被探测，对位点突变进行先验的定量预测。酶执行其设计的催化作用的微观机制的表征是现代酶学的中心焦点。获得这些详细信息对于预测酶的行为至关重要，对于设计新酶或修改现有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。

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.