ABSTRACT
The effect of lipid modification on polyethylenimine (PEI)-mediated DNA attraction was studied by performing umbrella sampling molecular dynamics simulations that involved PEIs modified with three different types of lipids: oleic acid (OA), linoleic acid (LA), and caprylic acid (CA). The potential of mean force between two DNA molecules in the presence of these lipid-modified PEIs was calculated using the weighted histogram analysis method, and it predicted the stability and size of the DNA aggregate. When compared to native PEI, lipid modification was found to enhance the stability of DNA aggregation in the case of long lipids (LA and OA) but reduce the stability in the case of a short lipid (CA). In addition, LA-substituted PEI was shown to form stronger DNA aggregate than OA-substituted PEI, which correlates positively with previous experimental observations.
Subject(s)
DNA/chemistry , Lipids/chemistry , Molecular Dynamics Simulation , Polyethyleneimine/chemistry , Caprylates/chemistry , Linoleic Acid/chemistry , Oleic Acid/chemistryABSTRACT
The aggregation of DNA molecules induced by cationic polymers is of importance to applications in gene delivery. In this work, we performed a series of umbrella sampling molecular dynamics simulations to calculate the potential of mean force (PMF) between two DNA molecules in the presence of polyethylenimine (PEI) molecules using the weighted histogram analysis method. The distance between the centers of mass of the two DNAs was chosen as the reaction coordinate, and the location and depth of the global minimum in the PMF curve were used to gauge the compactness and stability of the formed aggregate. The effects of PEI to DNA charge ratio (N/P charge ratio) and protonation state of the PEI were investigated. The DNA aggregation was found to be more favorable at higher PEI/DNA charge ratios and higher PEI protonation ratios. As compared with small multivalent ions, PEIs give rise to stronger DNA attraction even with an N/P charge ratio at which the DNAs are overneutralized. The effect of changing the protonation ratio on the compactness of the aggregate is more prominent than changing the N/P charge ratio, while the depth of the PMF well is more strongly influenced by the N/P charge ratio.
