Studies of the reactivity of organic substrates with metalloenzymes or biomimetic catalysts using quantum chemistry, electronic structure and spectra, quantum mechanics/ molecular mechanics.
Simulations of intermolecular interactions in mesogens and biological molecules
Successfully resolved a controversy that was arisen from different sets of experiments by two research groups on the mechanism of C-H hydroxylation by cytochrome P450 enzymes. Recently, Rittle and Green (Science (2010) 330, 933) characterized the compound I of P450 and found that it perform C-H hydroxylation via rebound mechanism as explained by theory since 2002.
Explained the role of environment in catalytic reactions of P450 such electric field, water molecule etc.
Described the oxidation properties of several non-heme enzymes/ systems such as Bleomycin, Cystein Dioxygenase, N4py, Bntpen etc.
Characterized and suggested several potent oxidants of Polyoxometalate.
Suggested correlations between physical properties like ionization potential, bond dissociation energies of drug like molecules with reaction barrier of reactions involved in drug metabolism by cytochrome P450 enzymes.
Abstract OpenTox Asia 2019
Drug Metabolism by Cytochrome P450.
The cytochromes P450 (CYP 450) are important heme enzymes in the human body, which metabolize about 80% of the 200 most commonly, prescribed FDA approved drugs. The complexities that arise at the molecular level have driven the field of computational chemistry intensely and as a consequence many detailed theoretical studies into the mechanism and function of CYP 450 enzymes have been reported. These studies will be reviewed here and will try to show that what the basic reaction mechanisms are of substrate activation and the effects that determine the stereo- and regioselectivity of the reaction, the production of by-products in the reaction mechanism and the nature of the substrate and enzyme active site. The main focus of the talk will be the mechanism and function of cytochrome P450 enzymes as elucidated by computational approaches. The emphasis of talk will be mainly on importance the theoretical and computational modeling on drug metabolism that is of enormous value to pharmaceutical applications of human cytochrome P450 enzymes.
- D. Kumar et al. J. Am. Chem. Soc. 2010, 132, 7656.