| Living cells are enclosed by lipid membranes, and the inside of a cell is also subdivided into different functionally distinct membrane-bound compartments. To overcome the barrier the membranes pose for cellular trafficking between the outside and the inside, or between different compartments of the cell, nature has evolved elaborate ways of transporting targets across the membranes, utilizing specially designed protein machines. In this thesis, two protein-membrane systems involved in cellular trafficking are investigated. The first system consists of a family of membrane-sculpting proteins, BAR-domains, which can reshape lipid membranes. BAR domains possess a positively charged concave surface, which bends negatively charged membrane into high-curvature tubes and vesicles. Experiments have suggested that BAR domains bend membrane in teams by arranging themselves in lattice-like scaffolds. We have developed models describing membrane sculpting by BAR domains at four levels of resolutions. Multiscale simulations elucidated how different types of BAR domain lattices determine the membrane curvature generated. Formation of entire membrane tubes by BAR domain lattices over time scales of 200 microseconds was observed in molecular dynamics simulations using a simplified, or "coarse-grained" description. An all-atom simulation of a 2.3-million-atom system covering 0.3 microsecond probed the dynamics of one specific BAR domain lattice in atomic detail. The second system studied in this thesis is a protein called lactose permease (LacY), which transports lactose across the cell membrane. We have identified a crucial salt-bridge that might play role in controlling the access of the sugar to the protein, and probed the molecular and energetic details of lactose translocation across LacY using steered molecular dynamics simulations. |
