Molecular Dynamics Study of a Lipid−DNA Complex

Lipid−DNA complexes are of topical interest because of their potential for use as vectors in gene therapy. Herein, molecular dynamics simulations have been carried out to probe the nature of lipid−DNA interactions and thereby provide a complement to recent experimental and theoretical studies. Specifically, we have investigated the DNA duplex d(CCAACGTTGG)2, in its canonical B-form, intercalated into a lipid bilayer consisting of a neutralizing binary mixture of cationic (dimyristoyltrimethylammonium propaneDMTAP) and zwitterionic (dimyristoylphosphatidylcholineDMPC) lipids. Surprisingly, both lipids are involved in neutralizing the anionic DNA phosphate groups. The electrostatic interactions between the cationic trimethylammonium (TAP) and zwitterionic phosphocholine (PC) headgroups of the two lipids allow the PC headgroups to orient out of the bilayer plane and thereby also become available to screen the negative charges on the DNA.