Theoretical Modeling of Enzyme Catalysis with Focus on Radical Chemistry

Abstract: Hybrid density functional theory (DFT) B3LYP method is applied to study the four diverse enzyme systems: zinc-containing peptidases (thermolysin and stromelysin), methyl-coenzyme M reductase, ribonucleotide reductases (classes I and III), and superoxide dismutases (Cu,Zn- and Ni-dependent enzymes). Powerfull tools of modern quantum chemistry are used to address the questions of biological pathways at their molecular level, proposing a novel mechanism for methane production by methyl-coenzyme M reductase and providing additional insights into hydrolysis by zinc peptidases, substrate conversion by ribonucleotide reductases, and biological superoxide dismutation. Catalysis by these enzymes, with the exception of zinc peptidases, involves radical chemistry.