Abstract
DNA-lipid complexes are of biomedical importance as delivery vectors for gene therapy. To gain insight into the interactions of DNA with zwitterionic and cationic (dimyristoyltrimethylammonium propane (DMTAP)) lipids, we have used coarse-grained molecular dynamics simulations to study the self-assembly of DPPC and DPPC/DMTAP lipid bilayers in the presence of a DNA dodecamer. We observed the spontaneous formation of lipid bilayers from initial systems containing randomly placed lipids, water-counterions and DNA. In both the DPPC and DPPC/DMTAP simulations, the DNA molecule is located at the water-lipid headgroup interface, lying approximately parallel to the plane of the bilayer. We have also calculated the potential of mean force for transferring a DNA dodecamer through a DPPC/DMTAP bilayer. A high energetic barrier to DNA insertion into the hydrophobic core of the bilayer is observed. The DNA adopts a transmembrane orientation only in this region. Local bilayer deformation in the vicinity of the DNA molecule is observed, largely as a result of the DNA-DMTAP headgroup attraction.