Scramblases are proteins that facilitate the movement of lipids between the two halves of cellular membranes. Despite recent interest towards understanding their structures and function, major knowledge gaps still remain. In this project, we look for so-far unidentified scramblases and resolve the role of the host membrane in regulating scramblase activity. Then, we proceed to design a novel pH-activated scramblase, which we embed into lipid vesicles that serve as early prototypes for drug delivery vehicles (DVVs). Our work is based on high-throughput molecular dynamics simulations, which allow the simultaneous scan of thousands of proteins or thousands of distinct lipid environments. The generated data are analysed using machine learning approaches to reveal both universal trends in scramblase function, as well as scramblase-specific selectivity patterns. Our computational findings will be validated by our international network of experimental collaborators.

2026

2030