Multiscsale simulations of membrane-membrane interfaces (360G-Wellcome-203815_Z_16_A)

Many fundamental cell biological processes take place at the juxtaposition of two membranes. Having methods for examining such systems is therefore of considerable interest, but few experimental techniques have the required spatial and temporal resolutions. Molecular dynamics (MD) simulations can theoretically offer insight into the time-dependent behaviour of membrane interfaces at near-atomic detail. In this work, we will develop the methodology for investigating membrane interfaces using multiscale MD simulations. During the first stage of the project, we will use a structurally and experimentally well-characterised system to develop and refine the methodological underpinnings of the simulation work. Specifically, we will use the available data on the myelin-axon interface bridged by myelin-associated glycoprotein (MAG) and its cognate ganglioside. Once the model is established, we will use it to address specific questions about this system, including the energetics of ganglioside binding, and the roles of various MAG post-translational modifications, including an unusual Trp C-mannosylation in the ganglioside-binding domain.