Quantum chemical studies of biochemical reaction mechanisms

SNIC 2017/1-590


SNAC Medium

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 (Density Functional Theory, DFT) are used to study biochemical model systems. Our group is world leading in this field, and our approach to quantum biomodeling is generally adopted as an important tool, as can be seen from the large number of citations (530) of an early (2000) description of this approach, as well as the 155 citations of a more recent review (2014). My main project concerns mechanisms for reduction of molecular oxygen and proton pumping in cytochrome c oxidase (CcO), the terminal enzyme in the respiratory chain where oxygen is reduced to water. We have suggested a gating mechanism for proton pumping against the gradient, which can explain many important experimental observations, and which is now further developed based on continued DFT calculations on larger and better models. Another enzyme of particular interest is nitric oxide reductase (NOR), since it has large similarities to cytochrome c oxidase. The first crystal structure of this enzyme was solved in 2010. Based on DFT calculations on the active site taken from the crystal structure, we have suggested a reaction mechanisms of NOR, which also can explain why this enzyme is non-electrogenic. CcO and NOR belong to the same family of enzymes and certain species can use both substrates, molecular oxygen and nitric oxide as substrate. An important approach to learn more about the reaction mechanisms is to make comparisons between the two enzymes for both substrates. Recently we published a mechanism for oxygen reduction in NOR. At present calculations are performed for NO reduction in CcO. During last year I started closer collaborations with the experimental groups working on these enzymes at Stockholm University, which has turned out to be very fruitful.