Thyveetil Mary-Ann, Coveney Peter V, Greenwell H Chris, Suter James L
Centre for Computational Science, Department of Chemistry, University College London, 20 Gordon Street, London WC1H 0AJ, United Kingdom.
J Am Chem Soc. 2008 Apr 9;130(14):4742-56. doi: 10.1021/ja077679s. Epub 2008 Mar 18.
The intercalation of DNA into layered double hydroxides (LDHs) has various applications, including drug delivery for gene therapy and origins of life studies. The nanoscale dimensions of the interlayer region make the exact conformation of the intercalated DNA difficult to elucidate experimentally. We use molecular dynamics techniques, performed on high performance supercomputing grids, to carry out large-scale simulations of double stranded, linear and plasmid DNA up to 480 base pairs in length intercalated within a magnesium-aluminum LDH. Currently only limited experimental data have been reported for these systems. Our models are found to be in agreement with experimental observations, according to which hydration is a crucial factor in determining the structural stability of DNA. Phosphate backbone groups are found to align with aluminum lattice positions. At elevated temperatures and pressures, relevant to origins of life studies which maintain that the earliest life forms originated around deep ocean hydrothermal vents, the structural stability of LDH-intercalated DNA is substantially enhanced as compared to DNA in bulk water. We also discuss how the materials properties of the LDH are modified due to DNA intercalation.
将DNA插入层状双氢氧化物（LDHs）有多种应用，包括用于基因治疗的药物递送和生命起源研究。层间区域的纳米尺度使得插入的DNA的确切构象难以通过实验阐明。我们利用在高性能超级计算网格上进行的分子动力学技术，对插入镁铝LDH中的长达480个碱基对的双链线性和质粒DNA进行大规模模拟。目前关于这些系统的实验数据报道有限。我们发现我们的模型与实验观察结果一致，根据实验观察，水合作用是决定DNA结构稳定性的关键因素。发现磷酸主链基团与铝晶格位置对齐。在与生命起源研究相关的高温高压条件下（生命起源研究认为最早的生命形式起源于深海热液喷口附近），与在大量水中的DNA相比，LDH插入的DNA的结构稳定性显著增强。我们还讨论了由于DNA插入导致LDH的材料特性如何被改变。
