By breathing life into macromolecular structures through molecular dynamics simulations we may assess the association of lipids, drug molecules and other components of protein complexes
One of the fundamental challenges in biological sciences is to visualise the dynamics of biomolecular machines in high-resolution detail. My group uses computational approaches to study membrane protein structures, from molecular modelling and multiscale molecular dynamics (MD) simulations, to bioinformatics methods such as covariance analysis. There are three primary themes that my group are pursuing:
Theme 1: Bacterial Biogenesis Pathways for Maturation and Localisation
With the increasing threat of anti-microbial resistance, we are especially interested in bacterial membrane proteins. Knowledge of the three-dimensional structures and dynamics of proteins involved in essential processes provides the physical details of potentially viable targets for killing drug-resistant, pathogenic bacteria.
Theme 2: Resource and Methodology Development for Membrane Proteins
Membrane proteins are of general interest due to their fundamental roles in cell biology. They also comprise ca. 25% of the proteome for the majority of organisms, and are targets for ca. 50% of the current pharmaceutical portfolio of small molecules. See MemProtMD for our collection of membrane protein structures embedded in lipid membranes: http://memprotmd.bioch.ox.ac.uk.
Theme 3: Multi-scale Simulations of Ion Channels and their relatives
Ion channels are essential for all life on Earth. The opening and closing of these tiny gated pores underlies everything that we do. Your ability to read this page, to move your limbs, to think and speak is down to the activity of ion channels. A multitude of medicinal drugs work by regulating the activity of these molecular machines, and impaired ion channel function is responsible for many human and animal diseases.