Lipid properties and the orientation of aromatic residues in OmpF, influenza M2, and alamethicin systems: Molecular dynamics simulations

Molecular dynamics simulations allow a direct study of the structure and dy namics of membrane proteins and lipids. We describe the behavior of aromati c residues and lipid properties in POPE and POPC bilayer models with the Es cherichia coli OmpF trimer, single alamethicin and Influenza M2 helices, 4- helix M2 bundles, and two alamethicin 6-helix channel models. The total sim ulation time is over 24 ns, of systems containing solvent, protein, and bet ween 104 and 318 lipids. Various types of adjustment between lipids and pro teins occur, depending on the size of the protein and the degree of hydroph obic mismatch between lipid and protein. Single helices cause little measur able effect on nearby lipids whereas the 4-helix bundles, 6-helix channel m odels, and OmpF cause a significant lowering of order parameters in nearby lipid chains, an increased difference between odd and even chain dihedrals in the magnitude of the trans dihedral fractions and dihedral transition ra tes, and in most cases a decreased gauche population and a decrease in bila yer thickness. An increased tilt of the lipid chains near the proteins can account for most of the observed decrease in order parameters. The orientat ion of tryptophans and tyrosines on the outside of the proteins is determin ed by packing at the protein exterior and non-specific hydrogen bonding wit h lipids and solvent. The tyrosines in the broad bands that delimit the hyd rophobic exterior of OmpF show little change in orientation over one nanose cond. Their rings are oriented predominantly perpendicular to the bilayer p lane, with the hydroxyl group pointing toward the lipid-water interface. Ph enylalanines in OmpF, alamethicin, and Influenza M2 are more mobile and ass ume a variety of orientations.