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

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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.