QM/MM Approach for Elucidating the Reaction Mechanisms of Heme and Nonheme Enzymes

Warshel and Levitt’sidea of quantum mechanical/molecular mechanical (QM/MM)approach has opened the door to model complex chemical systems such as enzymes and probe their reaction mechanisms. This approach combines a QM level of theory to describe the site where chemical reactions or electronic excitations occur and classical force field MM level to capture effects of the environment. In the recent times, state-of-the-art in QM/MM method gained immense importance as it provided high-accurate barriers, atomistic-level insights on mechanistic proposals, spectroscopic properties, and effects of mutations on reactivity of enzymes.

In the present talk I will focus on the highlights of the approach and the insights obtained recently in understanding the insilico mutation of F429H of heme (CYP 2B4) enzyme and reveal a novelDNA repair mechanism by AlkB a nonheme enzyme. Besides, I will discuss briefly my future interest in using this approach to understand the fundamental process in biological catalysts of oxidative enzymes that have broad academic and industrial applications.