Mapping the phase diagram of the writhe of DNA nanocircles using atomistic molecular dynamics simulations
Mapping the phase diagram of the writhe of DNA nanocircles using atomistic molecular dynamics simulations
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DOI：
10.1093/nar/gkm891
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发表时间：
2008-01-01
影响因子：
14.9
通讯作者：
Liverpool, Tanniemola B.
中科院分区：
文献类型：
--
作者：
Harris, Sarah A.;Laughton, Charles A.;Liverpool, Tanniemola B.
利用原子分子动力学模拟研究了双链体长度、序列、盐浓度和超螺旋密度对含178个碱基对的DNA纳米环构象的影响。这些计算揭示了扭曲和扭动的划分是由相互竞争的能量项的微妙平衡所支配的。我们已经确定了有利于环状，正或负扭曲和变性DNA构象的条件。我们的模拟结果表明，AT丰富的DNA更容易变性时，受到扭转应力比相应的GC含有圈。与简单的弹性棒预期的行为相反，在上缠绕和下缠绕的DNA纳米环的行为中存在明显的不对称性。生物学上最相关的负扭体状态比相应的正扭体构象更难以捉摸，并且仅在高静电屏蔽条件下观察到较大的圆。模拟结果已被总结通过绘制一个相图描述的各种构象状态的nanocircles在研究过程中探索的圆的大小和实验条件的范围内。伴随超螺旋的DNA结构的变化提示了许多机制，由此体内DNA拓扑结构的变化可能用于影响基因表达。
We have investigated the effects of duplex length, sequence, salt concentration and superhelical density on the conformation of DNA nanocircles containing up to 178 base pairs using atomistic molecular dynamics simulation. These calculations reveal that the partitioning of twist and writhe is governed by a delicate balance of competing energetic terms. We have identified conditions which favour circular, positively or negatively writhed and denatured DNA conformations. Our simulations show that AT-rich DNA is more prone to denaturation when subjected to torsional stress than the corresponding GC containing circles. In contrast to the behaviour expected for a simple elastic rod, there is a distinct asymmetry in the behaviour of over and under-wound DNA nanocircles. The most biologically relevant negatively writhed state is more elusive than the corresponding positively writhed conformation, and is only observed for larger circles under conditions of high electrostatic screening. The simulation results have been summarised by plotting a phase diagram describing the various conformational states of nanocircles over the range of circle sizes and experimental conditions explored during the study. The changes in DNA structure that accompany supercoiling suggest a number of mechanisms whereby changes in DNA topology in vivo might be used to influence gene expression.