Quantum chemical studies of biochemical reaction mechanisms
Title: Quantum chemical studies of biochemical reaction mechanisms
DNr: SNIC 2014/1-376
Project Type: SNIC Medium Compute
Principal Investigator: Margareta Blomberg <margareta.blomberg@su.se>
Affiliation: Stockholms universitet
Duration: 2015-01-01 – 2016-01-01
Classification: 10407
Keywords:

Abstract

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 (492) of an early (2000) description of this approach. 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. Recently very exciting new results were obtained for the mechanism and energetics of the CcO reaction. The new results explain seemingly conflicting experimental results. The new mechanism needs further development 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. One important remaining question is to elucidate if NOR from different species have different energy storage abilities, which has been indicated by recent experimental results. In collaboration with Shilu Chen mechanisms for nickel and cobalt containing enzymes are also investigated using DFT calculations.