Current research projects include:
The SecA Protein Motor
SecA is an essential component of the Sec translocation system in bacteria. SecA recognises the signal peptide of newly synthesised proteins destined for export, and couples the hydrolysis of adenosine triphosphate (ATP) with large-scale conformational changes to transport proteins across the plasma membrane; toxins are among the proteins secreted via the SecA path in bacteria. We employ computer simulations at the classical and combined quantum mechanical/molecular mechanical levels to understand the mechanism of the coupling between the chemical reaction (ATP hydrolysis), binding of the signal peptide and large-scale conformational changes of SecA.
Ion Pumps and Channels
Ion pumps are key components of living cells. These membrane-embedded proteins couple a reaction that yields energy (for example, the hydrolysis of ATP) with the uphill transport of ions across cellular membranes. We are particularly interested in understanding the mechanism of P-type ATPases, proteins that couple the hydrolysis of ATP and the phosporylation of an aspartic residue (hence the name ‘P-type’) with large-scale conformational changes to transport cations across cellular membranes.
Channelrhodopsin-2 is a light-gated cation channel that can be used as a powerful tool to probe neuronal circuits. Several amino acids critical for the ion pumping or sensory activity of other microbial-type rhodopsins are replaced in channelrhodopsin-2, where they are likely implicated in function. We use homology modelling and classical molecular dynamics computations to understand the functional role of specific interactions in channelrhodopsin-2.