| The overall aim is to understand the mechanism by which atomic interactions between various lipid and peptide components leads to the self-organisation of functional membrane sub-structures such as lipid "rafts" and transmembrane pores. Self-organisation is critical to cell function. Lateral domain formation, for example, can trigger membrane fusion and/or budding events as well as resulting in the sorting and transport of lipids and proteins. Peptide aggregation within the membrane can induce pore formation, membrane fusion, or lead to cell lysis. Little is known regarding the precise mechanism by which self-organisation in membranes occurs, or the specific roles of individual membrane constituents. This is because studying such dynamic processes at an atomic level experimentally is difficult and because self-assembly is a collective property dependent on the interactions between many constituents. Though difficult to study by experiment, self-assembly is amenable to study by molecular dynamics (MD) simulation techniques. MD simulations are being increasingly used to elucidate the properties of lipid bilayers and to study the interaction of various peptides and proteins with the lipid matrix. In particular, we have recently shown that it is possible to simulate the spontaneous self-assembly of lipid systems. This has provided us with a new and unique means of determining the nature of interactions in mixed systems. This we will exploit in these studies. There are three main elements of innovation: 1) the use of simulation techniques to study the molecular basis of self-organisation within membranes, 2) the combination of atomistic and coarse grained simulations and 3) the application of these computational techniques to realistic biological membranes. The project will integrate advanced computational methods together with knowledge of the chemical and physical properties of the membrane constituents in order to reproduce in detail the macroscopic properties of cell membrane systems. |
