All-atom Molecular Simulations to Probe Structure and Dynamics of Bacterial Membranes and Membrane-associated Proteins

Jeffery Klauda (University of Maryland)

Cellular biomembranes are essential to life by preventing unwanted molecules into a cell and allowing others to traverse the membrane (typically via integral or peripheral membrane proteins). Our research involves atomic-level molecular dynamics (MD) simulations of membranes with lipids alone and with proteins. We are currently developing accurate lipid force fields that compare favorably with available experiments on lipid bilayer structure (x-ray/neutron scattering and deuterium order parameters) and dynamics (diffusion and NMR relaxation times). One focus in the lab is developing accurate membrane models for various organisms and organelles within cells. These models go beyond standard studies of simple membrane models of two to three lipid types and aim to include important lipids for various organisms. As an example, cytoplasmic membrane models for E. coli with cyclic lipid moieties will be discussed and compared with simple models that have been used previously. These results indicate that simple models may deviate significantly for structural and elastic properties of in vivo bacterial membranes.

Lipids play an important structural role for cellular membranes but membrane-associated proteins are the main vehicles for substrate transport. A new, novel, and unbiased method for enhancing conformational timescales of secondary active transporters (SATs) will be presented that can probe conformations in the transport cycle of SAT proteins at atomic resolution. Comparisons will be made with two well-studied SAT proteins, i.e., lactose permease (LacY) and hydantoin permease (Mhp1). In addition to our studies on integral membrane proteins, microsecond simulations of a peripheral membrane protein (Osh4) involved in sterol and signaling lipid transport will be presented.

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