Title: Insights onto the Extraction of a Lipid from a Membrane using Molecular Dynamics Simulations
Abstract: In this study, we performed Molecular Dynamics simulations to determine the free energy profile in order to elucidate the interactions involved when extracting a lipid molecule from a lipid bilayer. Simulations of a POPC membrane containing a modified DOPE lipid (a model system for the biotinylated DOPE lipids used in AFM experiments) were performed using the Gromacs software package. The modified lipid molecule is first pulled out of the membrane at constant rate to certain z-positions normal to the membrane surface. Umbrella sampling simulations starting from those specific z-positions are then used to reconstruct a potential of mean force where the distance between the pulled lipid and the membrane is used as reaction coordinate. The simulations allow us to determine the factors (e.g. interfacial interactions, enthalpic/entropic contributions) affecting the free energy profile and the force needed to extract a lipid molecule from the membrane. These results are relevant for understanding processes involving hydrolytic, interfacially active enzymes where lipids need to be extracted before the enzyme can perform its function. We also studied the interactions between the antimicrobial magainin homolog MG-H2 with a POPC bilayer and its effect on the free energy profile of extracting the lipid molecule from the membrane.