Large Scale Molecular Dynamics Simulations to Explore Protein Binding and Lipid Reorganization on Membranes

Bacterial pore forming toxins (PFTs) oligomerize in the target cell membrane by forming nanometer sized pores (5-30 nm) and are responsible for gastrointestinal as well as virulent infections such as anthrax and diphtheria. Challenges lie in deciphering the driving force for membrane binding, lipid reorganization, role of extracellular domains and pathways during pore formation. In the case of  Listeriolysin O (LLO), which is a cholesterol dependent cytolysin (CDC), although the role of cholesterol has been implicated in its function the molecular details of the interaction are not completely understood. Experimental investigations do not probe the influence on lipid reorganization and membrane structure and dynamics during pore formation. The primary focus of this project is to use large-scale molecular dynamics simulations to understand cholesterol and lipid reorganization and dynamical heterogeneity on membranes due to PFT action.