Home › Faculty and Research › Faculty and Topics › Bioinformatics

Bioinformatics

Research area: 
Understanding mitochondrial processes by using computer modelling and simulation.
Group leader: 
Alan Robinson

The physiology of the mitochondrion arises from the dynamic interaction of networks of genes, proteins, and metabolites. We are using computers to model and simulate mitochondrial proteins and processes to understand the physiology of mitochondria in normal and disease states. Our specific research interests include, establishing the substrate binding and translocation mechanism of the mitochondrial carriers (see Figure), using virtual screening and molecular modelling to find protein inhbitors of therapeutic value, investigating the comparative and ab initio modelling of membrane proteins, and building models of mitochondrial physiology and metabolism. We also maintain the MitoMiner database of the mitochondrial proteome.

The predicted binding sites of the ornithine carrier, aspartate/glutamate carrier, carnitine/acetylcarnitine carrier, and oxoglutarate transporter, and their substrates docking to them.
[If the video appears to stall, drag the slider bar a little to the right and press 'play' again.]

Background information

Membrane protein structure

We are predicting the structures of membrane proteins and working out how they carry out their functions.

Mitochondrial protein ligands

We are making predictions about the substrates of uncharacterised mitochondrial transporters and designing inhibitors in silico.

Mitochondrial proteomics

We are characterising the proteome of the mitochondrion and building computer models of its metabolism in healthy and diseased states.

Selected publications

Ashrafian, H., Czibik, G., Bellahcene, M., Smith, A. C., Aksentijević, D., Sarah J Mitchell, S. J., Dodd, Jennifer Kirwan, Yavari, A., Støttrup, N. B., Contractor, H., Isackson, H., Cahill, T. J., Sahgal, N., Ball, D. R., Toftegaard Nielsen, T., Kharbanda, R. K., Neubauer, S., Redwood, C., de Cabo, R., Ahmet, I., Talan, M., Robinson, A. J. Viant, M. R., Pollard, P. J., Tyler, D. J. Watkins, H (2012).
Fumarate exerts cardioprotective effects via activation of the Nrf2-heme oxygenase antioxidant pathway
Cell Metab., 15, 361-371.

Smith, A. C., Blackshaw, J. A. and Robinson, A. J. (2011).
MitoMiner: a data warehouse for mitochondrial proteomics data
Nucleic Acids Res., 40, 1160-1167.

Smith, A., C. & Robinson, A., J. (2011).
A metabolic model of the mitochondrion and its use in modeling diseases of the tricarboxylic acid cycle..
BMC Syst. Biol., 5, 102-.

Smith, A. C. & Robinson, A. J. (2009).
MitoMiner: an integrated database for the storage and analysis of mitochondrial proteomics data
Mol. Cell. Proteomics 9, 1324-1337.

Robinson, A. J., Overy, C. & Kunji, E. R. S. (2008).
The mechanism of transport by mitochondrial carriers based on analysis of symmetry
Proc. Natl. Acad. Sci. U. S. A., 105, 17766-17771.

Monné, M., Robinson, A. J., Boes, C., Harbour, M. E., Fearnley, I. M. & Kunji, E. R. S. (2007).
The mimivirus genome encodes a mitochondrial carrier that transports dATP and dTTP
J. Virol., 81, 3181-3186.

Kunji, E. R. S. & Robinson, A. J. (2006).
The conserved substrate binding site of mitochondrial carriers
Biochim. Biophys. Acta 1757, 1237-1248.

Robinson, A. J. & Kunji, E. R. S. (2006).
Mitochondrial carriers in the cytoplasmic state have a common substrate binding site
Proc. Natl. Acad. Sci. U. S. A., 103, 2617-2622.