Quantum chemical studies of biochemical reaction mechanisms

NAISS 2023/22-35


NAISS Small Compute

Principal Investigator:

Margareta Blomberg


Stockholms universitet

Start Date:


End Date:


Primary Classification:

10407: Theoretical Chemistry




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. Concerning the basic mechanisms for both these enzymes, the calculations have elucidated several new mechanistic aspects. However, for the NO reduction there is still no consensus regarding which mechanism is actually followed. I have a close collaboration with the experimental groups working on these enzymes at Stockholm University (Peter Brzezinski and Pia Ädelroth), which has turned out to be very fruitful. In particular, further studies on the NO reduction in cNOR will be performed in collaboration with Pia Ädelroth, with both calculations and experiments. Recently I have started to study mechanisms also for other enzymes forming nitrous oxide from nitric oxide, starting with the flavin dependent non-heme diiron proteins (FDPs). For the FDPs there is important experimental information available, but there is no consensus on the reaction mechanism. My calculations have given strong evidence for one type of mechanism, and the description of the reaction path agrees with the most important experimental information. A paper on this is now accepted for the journal ACS Catalysis. Similar to the heme-Cu oxidases, the FDPs can perform both NO and oxygen reduction, and I have now started to study also the mechanism for the oxygen reduction.