Molecular dynamic simulation of fluoxetine partitioning into 1,2 - dioleoyl - SN- glycero- 3- phosphochline (DOPC) bilayer

Abstract

Fluoxetine is a wide prescribed antidepressant that has been commercially available for decades; however, the underlying mechanism is still unclear. While its interaction with serotonin receptors is crucial, the effect comes from the interaction with the plasma membrane is not negligible. Possessing the properties of an amphiphilic drug, its complicated activities cannot be simply described by biological nor mechanical mean alone. The presence of a thermodynamic profile can be used in couple with clinical researches to shed light on further implications. Yet such a profile is not available due to the limit in non-invasive methods to explore these properties. Molecular dynamic simulation is one of the most popular computational methods that harness the physical model and computing power to calculate these parameters in silico. In this study, molecular dynamics is used to simulate the process of fluoxetine partitioning into DOPC bilayer. Gibbs free energy (ΔG), enthalpy (ΔH), entropy (ΔS) and orientation of fluoxetine in the process is examined. The result suggests that fluoxetine is favorable in the hydrophobic region of the lipid tail. This process is spontaneous at low temperature and is going to be non-spontaneous at a higher temperature. The consistent free energy and orientation result implies that fluoxetine hydrogen interaction is maximized under the hydrophobic effect of the surrounding lipid tail. Keywords: Lipid bilayer, Antidepressant, Molecular Dynamics and Thermodynamics