Role of the central cations in the mechanical unfolding of DNA and RNA G-quadruplexes.
Role of the central cations in the mechanical unfolding of DNA and RNA G-quadruplexes.
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DOI：
10.1093/nar/gkv690
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发表时间：
2015-09-03
影响因子：
14.9
通讯作者：
Falo F
中科院分区：
文献类型：
--
作者：
Bergues-Pupo AE;Arias-Gonzalez JR;Morón MC;Fiasconaro A;Falo F
众所周知，阳离子在核酸双链中可以调节不同的相互作用，但它们在四链结构的排列中是关键的。在这里，我们使用显式溶剂的全原子分子动力学模拟来分析典型的分子内G-四链结构的机械去折叠：在稳定阳离子存在的情况下，平行、杂交和反平行的DNA和平行的RNA。我们证实了这些构象在中心离子存在的情况下的稳定性，并在它们不存在的情况下观察到了四元体拓扑的扭曲。然后研究了力诱导的展开动力学。我们发现，力-伸展曲线中的展开事件伴随着中心离子与G-四链体中鸟嘌呤之间配位的丧失。我们发现平行构型相对于反平行构型的破裂力更低，而平行RNA力模式的行为似乎类似于平行DNA。我们预计，我们的结果将对解释高分辨率拉伸分析中的精细结构破裂轮廓至关重要，并将阐明G-四链结合机械的机械力化学活性。
Cations are known to mediate diverse interactions in nucleic acids duplexes but they are critical in the arrangement of four-stranded structures. Here, we use all-atom molecular dynamics simulations with explicit solvent to analyse the mechanical unfolding of representative intramolecular G-quadruplex structures: a parallel, a hybrid and an antiparallel DNA and a parallel RNA, in the presence of stabilising cations. We confirm the stability of these conformations in the presence of central ions and observe distortions from the tetrad topology in their absence. Force-induced unfolding dynamics is then investigated. We show that the unfolding events in the force-extension curves are concomitant to the loss of coordination between the central ions and the guanines of the G-quadruplex. We found lower ruptures forces for the parallel configuration with respect to the antiparallel one, while the behaviour of the force pattern of the parallel RNA appears similar to the parallel DNA. We anticipate that our results will be essential to interpret the fine structure rupture profiles in stretching assays at high resolution and will shed light on the mechanochemical activity of G-quadruplex-binding machinery.