Structural Flexibility of DNA-RNA Hybrid Duplex: Stretching and Twist-Stretch Coupling

DNA-RNA hybrid (DRH) duplexes play essential roles during the replication of DNA and the reverse transcription of RNA viruses, and their flexibility is important for their biological functions. Recent experiments indicated that A-form RNA and B-form DNA have a strikingly different flexibility in stretching and twist-stretch coupling, and the structural flexibility of DRH duplex is of great interest, especially in stretching and twist-stretch coupling. In this work, we performed microsecond all-atom molecular dynamics simulations with new AMBER force fields to characterize the structural flexibility of DRH duplex in stretching and twist-stretch coupling. We have calculated all the helical parameters, stretch modulus, and twist-stretch coupling parameters for the DRH duplex. First, our analyses on structure suggest that the DRH duplex exhibits an intermediate conformation between A-and B-forms and closer to A-form, which can be attributed to the stronger rigidity of the RNA strand than the DNA strand. Second, our calculations show that the DRH duplex has the stretch modulus of 834 +/- 34 pN and a very weak twist-stretch coupling. Our quantitative analyses indicate that, compared with DNA and RNA duplexes, the different flexibility of the DRH duplex in stretching and twist-stretch coupling is mainly attributed to its apparently different basepair inclination in the helical structure.

DNA - RNA杂合（DRH）双链在DNA复制和RNA病毒逆转录过程中起着至关重要的作用，其柔韧性对其生物学功能非常重要。近期实验表明，A - 型RNA和B - 型DNA在拉伸及扭 - 拉耦合方面具有显著不同的柔韧性，DRH双链的结构柔韧性备受关注，尤其是在拉伸及扭 - 拉耦合方面。在这项工作中，我们利用新的AMBER力场进行了微秒级的全原子分子动力学模拟，以表征DRH双链在拉伸及扭 - 拉耦合方面的结构柔韧性。我们计算了DRH双链的所有螺旋参数、拉伸模量以及扭 - 拉耦合参数。首先，我们对结构的分析表明，DRH双链呈现出介于A - 型和B - 型之间且更接近A - 型的中间构象，这可归因于RNA链比DNA链具有更强的刚性。其次，我们的计算显示DRH双链的拉伸模量为834 ± 34皮牛，且扭 - 拉耦合非常弱。我们的定量分析表明，与DNA和RNA双链相比，DRH双链在拉伸及扭 - 拉耦合方面的不同柔韧性主要归因于其螺旋结构中碱基对倾斜度的明显差异。