Quantum chemical studies of biochemical reaction mechanisms
Title: Quantum chemical studies of biochemical reaction mechanisms
SNIC Project: SNIC 2021/5-609
Project Type: SNIC Medium Compute
Principal Investigator: Margareta Blomberg <margareta.blomberg@su.se>
Affiliation: Stockholms universitet
Duration: 2022-01-01 – 2023-01-01
Classification: 10407


The general goal of my research is to elucidate enzyme mechanisms, in particular for redox active enzymes containing transition metals. For this purpose quantum chemical methods (mainly hybrid Density Functional Theory, DFT) are used to study biochemical model systems. My main project concerns mechanisms for enzymes involved in cellular respiration. Therefore I study the reduction of molecular oxygen and proton pumping in cytochrome c oxidase (CcO), the terminal enzyme in the respiratory chain. Another enzyme belonging to the same family as CcO is nitric oxide reductase (cNOR), which reduces nitric oxide to nitrous oxide and water. The basic mechanisms for both these enzymes have been studied, and several new mechanistic aspects have been established in several publications. In recent years I have developed closer collaborations with the experimental groups working on these enzymes at Stockholm University, which has turned out to be very fruitful and resulted in several publications, and which will continue. Recently I have started to study mechanisms also for other enzymes forming nitrous oxide from nitric oxide, such as flavin dependent non-heme diiron proteins (FDPs) and hydroxyl amine oxidases (HAO). In particular for the FDPs there is important experimental information available, but there is no consensus on the reaction mechanism. Preliminary computational results have been obtained.