Physical and Theoretical Chemistry

Biography

Biography: Jiri Kozelka

Abstract

NAD-dependent formate dehydrogenase (FDH) uses NAD+ as cofactor to catalyze the oxidation of  formate to CO₂ (Figure 1). The interaction between the formate anion and NAD+ is a case of an anion-p interaction. It has expectedly a strong electrostatic component, however, the low-lying empty p orbitals of NAD+ make this oxidant also a potential acceptor for donor-acceptor covalent bonding. In the present work, we used two energy decomposition schemes, EDA1 and NEDA2 to monitor the physical nature of  the substrate-cofactor interaction during  the reaction (H-COO- + NAD+ ® CO₂ + NADH). The coordinates of the substrate-cofactor pair were taken from a QM/MM simulation of the reaction inside the Candida boidinii FDH by Guo et al.;3 these coordinates enabled us to study the interaction in the reactants state, transition state, and products state  in the conformation and orientation the reacting partners have in the active site of the enzyme.