Our pioneering work on enzyme catalysed hydrogen transfer (e.g. our recent article in Science) has led to a better understanding of enzyme mechanism by providing a new conceptual framework for enzyme catalysis. This has resulted in a paradigm shift away from standard "over the barrier" textbook models of enzyme catalysis to a "through the barrier" model, for which quantum tunnelling is invoked. We are using computational chemistry techniques to study factors controlling H-tunnelling in enzymes. We are investigating the importance of the nature of the energy barrier - the overall shape, rather than simply the height as with transition state theory - in controlling reaction rate. In addition to barrier shape, a key role has also been identified for enzyme motion in driving the tunnelling reaction - we are studying how this is coupled to (drives) the tunnelling event.

We are also studying the role of dynamics in interprotein electron transfer - in particular how dynamics facilitates electron transfer between partner proteins in weakly assembling electron transfer complexes. Additionally, we are studying the role of the protein environment in controlling the chemistry of redox cofactors.

Cytochromes P450 are highly reactive with a broad spectrum of organic compounds, and thus play a key role in the handling of xenobiotics within the cell. In particular, we are studying drug metabolism by human P450s and the catalytic role of P450s in Mycobacterium tuberculosis. Our in silico studies are producing predictive models of P450 substrate specificity and selectivity. Additionally, they are successfully guiding the re-engineering of enzyme function.

Many fundamental biological processes rely on the movement of K⁺ across cell membranes through K⁺ channels. We are studying the dynamics of, and ligand binding to, a range of K⁺ channels - in particular, factors at the atomic level that drive K⁺ channel gating and lead to drug block (particularly with hERG).