EFFECTS OF ANESTHETICS ON THE STRUCTURE OF A PHOSPHOLIPID-BILAYER - MOLECULAR-DYNAMICS INVESTIGATION OF HALOTHANE IN THE HYDRATED LIQUID-CRYSTAL PHASE OF DIPALMITOYLPHOSPHATIDYLCHOLINE

We report the results of constant temperature and pressure molecular d ynamics calculations carried out on the liquid crystal (L-alpha) phase of dipalmitoylphosphatidylcholine with a mole fraction of 6.5% haloth ane (2-3 MAC). The present results are compared with previous simulati ons for pure dipalmitoylphosphatidylcholine under the same conditions (Tu et al., 1995, Biophys. J. 69:2558-2562) and with various experimen tal data. We have found subtle structural changes in the lipid bilayer in the presence of the anesthetic compared with the pure lipid bilaye r: a small lateral expansion is accompanied by a modest contraction in the bilayer thickness. However, the overall increase in the system vo lume is found to be comparable to the molecular volume of the added an esthetic molecules. No significant change in the hydrocarbon chain con formations is apparent. The observed structural changes are in fair ag reement with NMR data corresponding to low anesthetic concentrations. We have found that halothane exhibits no specific binding to the lipid headgroup or to the acyl chains. No evidence is obtained for preferen tial orientation of halothane dynamics of the lipid-bound halothane mo lecules appears to et al., 1995.