MOLECULAR DYNAMICS SIMULATIONS OF DNA PARTITION IN CATIONIC LIPID BILAYERS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cationic lipids are used for delivery of plasmid DNA vectors in both experimental biology and medicine. In recent years, encouraging results have been obtained in gene therapy of cystic fibrosis, cancer, and cardiovascular diseases. However, understanding of the DNA delivery process is still limited and the low efficiency of lipid-based transfection is a concern. In understanding the machinery of DNA delivery, the question of how DNA associate and dissociates from the lipoplexes is clearly important. So far only one study of atomistic simulations of the DNA-lipid complex was conducted in 1999 for a total of 5.5 ns in a small system with only 48 lipid molecules. We propose to conduct atomistic molecular dynamics simulations of DNA association in DMPC bilayers with 128 lipid molecules for long simulations on the order of 100 ns. Our present study of PNA partitioning in lipid bilayer shows that the equilibration time is in such a timescale. We will estimate the free energy difference accompaning the DNA-lipid association. We will use NAMD, the open molecular dynamics simulation package (www.ks.uiuc.edu/Research/namd/), for our research. This package, recipient of a 2002 Gordon Bell Award, is a parallel molecular dynamics code designed for high-performance simulation of large biomolecular systems. Based on Charm++ parallel objects, NAMD scales to hundreds of processors on high-end parallel platforms.