De-novo protein design is an area of research that holds great potential for revolutionary advancement to diverse fields including medical therapeutics and bio-industrial processes. The design of membrane proteins has lagged behind advances made to soluble protein design in recent years due to the difficulties inherent to studying proteins in a membrane environment. As such the field still requires ground work to understand the basic principles that govern the interaction of transmembrane (TM) domains with each other and the bilayer environment.
We have taken a bottom up design approach to understanding these interactions, working from a TM helix of minimal sequence complexity and characterising, in depth, the effects that alterations and additions have on structure and behaviour. A range of techniques have been utilised for this process including in-vivo, in-vitro and in-silico approaches.
Nash, A., Notman, R. and Dixon, A. M. De novo design of transmembrane helix-helix interactions and measurement of stability in a biological membrane. Biochim. Biophys. Acta - Biomembr. 2015, 1848, 1248–1257