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RUI的一家机构，他得到了理论和计算化学计划以及分子生物物理计划的支持，利用从头算量子化学方法探索酶催化的反应机制。这项研究的第一个目标是全面了解核糖核酸酶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关于RNaseA的动力学和结构数据的比较，开发一种使用这种方法来表征其他酶机制的通用方法。一旦建立，就可以探索其他相关的酶系统，以做出关于位点突变的先验定量预测。酶执行其设计的催化作用的微观机制的特征是现代酶学的中心焦点。获得这样详细的信息对于预测酶的行为是至关重要的，对于设计新的酶或为特定的催化任务修改现有的酶是必不可少的。近年来，计算技术在这一努力中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.