About me....

Australian citizen. Entered Royal Melbourne Institute of Technology (RMIT) in 1995 as an undergraduate in Applied Chemistry, graduating with Honours in 1999. Deciding to quit chemistry while ahead, joined the Applied Physics department as a graduate student, completing a PhD thesis in computational minerals science in 2002. Joined the laboratory of Professor Mark Sansom, University of Oxford, as a postdoctoral researcher. Currently involved in molecular dynamics simulations of transmembrane proteins, as well as simulated compression of metalloproteins (see below). Research is currently carried out as part of the IRC Bionanotechnology.

Project Descriptions

1) MD Simulations of the Transmembrane Region of nAChR

AChR was the first receptor-mediated ion channel protein to be isolated and studied, and although numerous functional studies have been performed on this class of receptors, their atomic structures (and hence their mechanisms of function) have not been fully elucidated. Recently, a 4.0 Å resolution structure of the TM region of nAChR was published. The current aims are to perform MD simulations on this structure in a model lipid bilayer with a view to determine its gating mechanism and the pathway by which ligand-binding is transduced to channel gating.

Vector plot indicating atomic displacements of a normal mode for the M1, M2 and M3 helices of nAChR (left), and the physical dimensions along the pore in surface representation (computed using HOLE) (right).

2) Compressional Deformations of Metalloproteins (in collaboration with Jianwei Zhao and Jason J. Davis in the Department of Chemistry)

Previous studies of the conduction properties of the copper protein azurin were carried out using AFM, in which the tunneling conductance of the protein was measured as a function of applied tip force. In the current work, MD simulations have been performed in order to determine the structural evolution of the protein with respect to compression, which may help to explain the experimentally observed tunneling conduction behaviour.

3) Virtual Biosensors (in collaboration with Sylvanna Ho and the National Physical Laboratory "Single Molecule Detection" group )

Molecular biosensors combine a biological recognition mechanism with a physical transduction technique. The highly specific ligand recognition capabilities, efficient signal amplification, and stability of certain ion channel proteins make them attractive candidates for biosensor applications. An example is the AMBRI biosensor, which comprises the gramacidin ion channel embedded in a lipid bilayer, tethered to a gold electrode surface, with an antibody fragment attached to the extramembranous region of the peptide. Currently, we are developing models of simple biosensor systems that may be studied using molecular dynamics simulations. Of particular interest is the influence of the inorganic surface on the tethered protein and bilayer, and the stability of the system.

Some recent publications

Presentations

Links

Sansom group home page

National Physics Laboratory : Single Molecule Detection

Davis Group in the Department of Chemistry