Kachlishvili, Khatuna2012-06-282016-09-292011-05-31bibid: 7745246https://hdl.handle.net/1813/29374The methylene-interrupted, all-cis (Z) bond configuration is overwhelmingly favored in polyunsaturated fatty acids (PUFA) of vertebrate membranes, particularly the highly unsaturated membranes of electrically-active neural tissue. The hypothesis that hexaene and pentaene homoallylic groups are sterically allowed to follow the groove of a transmembrane [alpha]-helix from bovine rhodopsin using energy minimization (EM) and molecular dynamics (MD) simulations with the GROMOS96 force field was investigated. Docosahexaenoic acid (22:6n-3) and docosapentaenoic acid (22:5n-6) were configured along arbitrary, mid-, top-helix paths along helix 2, with the doubly allylic hydrogens directed inward and the ethylenic hydrogens directed out of the helix. It was shown, by performing EM and MD simulations for 22:6n-3 and 22:5n-6, that the rotationally constrained homoallylic regions are more stably contained within the groove than saturated regions. The analyses of the initial conformations of 22:6n3 in phosphatidylcholine-22:6n-3/34:5n-3 and 22:5n-6 in phosphatidylcholine-22:5n6/34:5n-3, and of conformations of 22:6n-3 in phosphatidylcholine-22:6n-3/34:5n-3 obtained after EM showed that the homoallylic regions fit loosely within the groove while the saturated regions are much closer to the groove boundary. Calculations using a configuration with phosphatidylcholine-22:6n-3/34:5n-3 showed that the 22:6n-3 chain can follow the groove nearest a membrane-water interface, while the homoallylic region of the very long chain 34:5n-3 can follow the groove nearer the membrane center, tethered by its extended saturated region. These results illustrate that the homoallylic polyunsaturated fatty acid motif is not sterically restricted from occupying the groove of a transmembrane [alpha]-helix and provide a testable prediction. The biophysical stability and properties conferred by this configuration was speculated.en-USGlycerophospholipidsDocosahexaenoic fatty acidDocosapentaenoic fatty aciddissertation or thesis