Understanding molecular motors through imaging and modelling

Dimeric coiled coils are formed by two alpha helices that wrap around each other to bury hydrophobic residues. They are found widely throughout the proteome, and have important mechanical roles in proteins. Intriguingly, it has recently been discovered when binding partners bind to proteins with long coiled coils they have a large influence on the mechanics and flexibility of the coiled coil, and the resulting change in flexibility is important for the biological function of the protein. But, how does this happen?
The aim of this project is to try to understand how small breaks, or discontinuities in the coiled coil affect the properties of the proteins that contain them, enabling them to transmit information and determine their biological function. This type of effect was recently shown for EEA1, an endosomal protein (Murray et al., Nature, 2016). This project will combine molecular dynamics simulations, a novel type of coarse grained simulation called FFEA, and laboratory experiments including expression of proteins and negative stain electron microscopy, to investigate long coiled coils, and what determines their flexibility and function.