Studies of membrane and membrane protein systems using molecular dynamics simulations

Molecular dynamics (MD) simulations have become a standard method to explore the detailed atomic properties of molecular systems. Several problems are studied pertaining to membranes and membrane protein systems. Firstly a pure lipid bilayer of di-myristoyl-phosphatidyl-choline (DMPC) is examined. The lateral diffusion coefficient of the lipids in the membrane plane is estimated from a 10 ns simulation. This is compared with previous experimental and simulation results. We also study the structure of the lipid water interface in order to gain a better understanding of the interfacial hydrogen-bonding properties. Secondly, all-atom simulations are employed to study structural and dynamical properties of viral protein U (VPU) from the Human Immunodeficiency Virus 1 (HIV) in a fully hydrated lipid palmitoyl-oleyl-phosphatidyl-ethanolamine (POPE) bilayer. Structural properties such as the tilt angle and position of the protein in the bilayer, and the role of amino acid groups that serve to anchor the membrane in the bilayer are reported. Results from our simulations suggest that specific amino acid groups can play a role in gating. Thirdly, the development and application of a new coarse grain model is reported. This model sacrifices detail to extend the accessible time and length scales. The parametrization procedure is discussed along with several applications. In order to assess the advantages and limitations of the model, a comparison with the previously mentioned all-atom DMPC simulations is performed. Self-assembly of phospholipids into several of their known thermodynamic phases is also reported. Finally, a study of the insertion of model nanopores and antimicrobials into lipid bilayer membranes employing the coarse grain model is reported