MOLECULAR DYNAMICS SIMULATIONS OF DNA PARTITION IN CATIONIC LIPID BILAYERS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 阳离子脂质在实验生物学和医学中用于质粒DNA载体的递送。近年来，囊性纤维化、癌症和心血管疾病的基因治疗取得了令人鼓舞的成果。然而，对DNA递送过程的理解仍然有限，并且基于脂质的转染的低效率是一个问题。在理解DNA传递机制时，DNA如何与脂质复合物结合和解离的问题显然很重要。到目前为止，只有一个研究的DNA-脂质复合物的原子模拟在1999年进行了总共5.5纳秒在一个小系统中只有48个脂质分子。我们建议进行原子分子动力学模拟的DNA协会在DMPC双层与128个脂质分子长模拟的顺序为100 ns。我们目前对PNA在脂质双层中分配的研究表明，平衡时间就是这样一个时间尺度。我们将估计DNA-脂质缔合的自由能差。我们将使用开放的分子动力学模拟软件包NAMD（www.ks.uiuc.edu/Research/namd/）进行研究。该软件包获得了2002年戈登·贝尔奖，是一个并行分子动力学代码，用于大型生物分子系统的高性能模拟。NAMD基于Charm++并行对象，可扩展到高端并行平台上的数百个处理器。

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.