Structure and Dynamics of Lipids, Model Cellular Membranes, and Membrane Proteins
September 30, Tue 2008
11:00 am, MRB 200 Conference Room
Dr. Jeffrey Klauda
Department of Chemical and Biomolecular Engineering, University of Maryland,
Biological membranes consist of a layered matrix of molecules that form a barrier to protect the cell from its environment and selectively control the entrance/exit of small molecules. We aim to utilize molecular simulations to elucidate the structure and dynamics of biological membranes, as well as small molecule transport to and through the lipid bilayer. Accurate lipid force fields are essential for such simulations of lipid bilayers. Extensive ab initio quantum mechanical (QM) calculations have been used to improve the CHARMM27 lipid force field. The QM-based changes resulted in simulations that agree with experimental deuterium order parameters and 13C NMR relaxation times. This new force field has been used to aid x-ray diffraction experiments in obtaining density profiles of liquid crystalline lipid bilayers. Although our initial studies were with pure lipid bilayers, we are currently investigating mixed lipid bilayers with cholesterol.
Although lipids are important structural components of the cellular membrane, proteins dynamically control the entrance/exit of small molecules to the membrane or cytoplasm. We are focusing on two such proteins â€“ a cholesterol transporter of yeast (Osh4) and a disaccharide transporter of E. coli, specifically lactose permease (LacY). Osh4 is a member of the OSH family of proteins that is believed to transport sterols from the endoplasmic reticulum to the plasma membrane. Molecular dynamic simulations of Osh4 and cholesterol suggest a dual molecular ladder mechanism for sterol release to the cytoplasm. LacY is member of the major facilitator superfamily of transmembrane proteins, which can transport a variety of small molecules from sugars to antibiotics. Our work in this area has been to describe disaccharide binding to the LacY and determine a protein structure that is open to the periplasm.