Molecular dynamics simulations of anesthetics in phospholipid bilayers

Since almost all biologically relevant cell membranes are formed by phospholipid bilayers, the investigation of the influence of anesthetics on the physical and chemical properties of these bilayers is essential for actually understanding the mechanism of anesthesia. In our research, molecular dynamics simulations of fully hydrated POPC bilayers containing the anesthetic ketamine in concentrations between 0 and 8% were performed. A variety of analysis methods were applied to the simulation data to obtain detailed information about membrane parameters that may change due to the presence of anesthetics. We especially focused our attention on the anesthetic induced variation of the lateral pressure profile, whose modification can effect membrane proteins like ion channels by changing their conformational equilibrium. The results clearly show that the anesthetic most likely resides at a certain height in the bilayer. Especially at that position, the lateral pressure gets more and more reduced with increasing concentrations, leading to relative differences of more than 10% compared to the unanesthetized membrane. The corresponding changes of the first and second moments of the lateral pressure applied to a simple geometric model of an ion channel confirm that the conformational equilibrium of the channel is significantly shifted even at low ketamine concentrations.5