We present a computer model which captures the self-assembly of cationic
liposomes complexed with DNA - a promising synthetically based nonviral
carrier of DNA for gene therapy. The model is a full molecular
description that allows the study of molecular self-assembly from
structural disorder. Computational simplifications necessary for
efficiency are introduced through a coarse-grained representation of the
intra-molecular atomic details. The inter-molecular potentials are
designed to mimic the hydrophobic effect without the explicit presence
of solvent. Thus, the approach carefully balances the need for molecular
detail with computational practicality in a manner that allows for
solvent-free simulations of complex self-assembly over long enough time
scales to address experimental reality. In addition to showing
spontaneous selfassembly of cationic lipid (CL)-DNA complexes, the broad
utility of the model is illustrated by demonstrating excellent agreement
with X-ray diffraction experimental data. We study the structural and
thermodynamic properties of complexes containing both monovalent and
multivalent CLs. In the latter case, the condensation of the DNA
molecules is greatly enhanced by attractive, CL-mediated, DNA-DNA
interactions. Examining published transfection efficiency (TE) data in
the light of our results supports a previously proposed hypothesis that
stability and TE of CL-DNA complexes are oppositely correlated.
