Stabilization of duplex DNA and RNA by dangling ends studied by free energy simulations.
Stabilization of duplex DNA and RNA by dangling ends studied by free energy simulations.
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DOI：
10.1002/bip.22398
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发表时间：
2014-04
期刊：
影响因子：
2.9
通讯作者：
M. Kara;M. Zacharias
中科院分区：
文献类型：
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作者：
M. Kara;M. Zacharias
双链核酸末端的单个未配对核苷酸，称为悬挂末端，可以促进双链稳定性。对双链和单链RNA和DNA分子末端悬挂的胞嘧啶和鸟嘌呤核苷酸进行了伞形抽样自由能模拟，研究了悬挂末端效应的分子起源。在不受限制的模拟中，悬挂的末端核苷酸保持在实验结构中观察到的位置附近。计算的与存在悬挂核苷酸相关的自由能贡献与预测嘌呤与嘧啶悬挂末端更稳定的总体趋势的实验是合理一致的。此外，计算表明，对于DNA，5‘端的悬挂末端比3’端的悬挂末端具有更显著的稳定作用，而对于RNA，则相反的趋势。静电和范德华相互作用都有助于悬垂末端核苷酸的双链稳定作用。自由能模拟方案也可用于设计能增强双链稳定性的悬垂末端核苷酸。
Single unpaired nucleotides at the end of double-stranded nucleic acids, termed dangling ends, can contribute to duplex stability. Umbrella sampling free energy simulations of dangling cytosine and guanine nucleotides at the end of duplex and single stranded RNA and DNA molecules have been used to investigate the molecular origin of dangling end effects. In unrestraint simulations, the dangling end nucleotides stayed close to placements observed in experimental structures. Calculated free energy contributions associated with the presence of dangling nucleotides were in reasonable agreement with experiment predicting the general trend of a more stabilizing effect of purine vs. pyrimidine dangling ends. In addition, the calculations indicate a more significant stabilizing effect of dangling ends at the 5'-end vs. 3'-end in case of DNA and the opposite trend in case of RNA. Both electrostatic and van der Waals interactions contribute to the duplex stabilizing effect of dangling end nucleotides. The free energy simulation scheme could also be used to design dangling end nucleotides that result in enhanced duplex stabilization.