Spanish scientists have used computational chemistry to follow oxygen's journey to the iron centre of hemes.

Heme proteins, such as hemoglobin and myoglobin, use heme groups to transport and store oxygen, functions that are important for respiration and metabolic processes in mammals. Although the proteins are well studied, the actual mechanism for attaching and releasing oxygen to and from heme groups is unknown. 

Understanding how oxygen interacts with heme is difficult because the molecules' many different electron configurations provide oxygen with several possible routes to bind to iron in the heme group. Now, Juan Novoa and Jordi Ribas-Ariño, at the University of Barcelona, have calculated the different electronic states of dioxygen and heme iron to work out the most favourable, lowest energy route for the binding process.

The calculations give insight into how dioxygen binds to hemes such as that found in deoxymyoglobin (above)

Novoa and Ribas-Ariño used ab initio methods to determine energy profiles for O₂ addition to deoxyheme and O₂ loss from oxyheme. Novoa explained: 'Because ab initio uses total energy calculations to model biological molecules, it is more accurate than the widely used density functional theory [DFT]. DFT relies only on electron density calculations, so the models it provides are more approximate.' The duo's calculations predicted a previously unknown low energy barrier pathway for the reaction, which matched experimental observations for reversible oxygen binding to hemoglobin and myoglobin. 

Jeremy Harvey an expert in computational chemistry at the University of Bristol, UK, described the work as exciting. 'It gives new insight into dioxygen-heme group binding. Ab initio methods, in principle, can give a more detailed and accurate description of the system than cheaper DFT,' he said.

Janet Crombie