School of Medical Engineering, Xinxiang Medical University, Xinxiang 453003, China.
School of Public Health, Hubei University of Medicine, Shiyan 442000, China.
Molecules. 2024 Oct 17;29(20):4920. doi: 10.3390/molecules29204920.
DNA-RNA hybrid duplexes play essential roles during the reverse transcription of RNA viruses and DNA replication. The opening and conformation changes of individual base pairs are critical to their biological functions. However, the microscopic mechanisms governing base pair closing and opening at the atomic level remain poorly understood. In this study, we investigated the thermodynamic and kinetic parameters of the dA-rU base pair in a DNA-RNA hybrid duplex using 4 μs all-atom molecular dynamics (MD) simulations at different temperatures. Our results showed that the thermodynamic parameters of the dA-rU base pair aligned with the predictions of the nearest-neighbor model and were close to those of the AU base pair in RNA. The temperature dependence of the average lifetimes of both the open and the closed states, as well as the transition path times, were obtained. The free-energy barrier for a single base pair opening and closing arises from an increase in enthalpy due to the disruption of the base-stacking interactions and hydrogen bonding, along with an entropy loss attributed to the accompanying restrictions, such as torsional angle constraints and solvent viscosity.
DNA-RNA 杂交双链在 RNA 病毒的逆转录和 DNA 复制过程中发挥着重要作用。单个碱基对的打开和构象变化对其生物功能至关重要。然而，在原子水平上控制碱基对关闭和打开的微观机制仍知之甚少。在这项研究中，我们使用不同温度下的 4 μs 全原子分子动力学 (MD) 模拟研究了 DNA-RNA 杂交双链中 dA-rU 碱基对的热力学和动力学参数。我们的结果表明，dA-rU 碱基对的热力学参数与最近邻模型的预测一致，并且与 RNA 中的 AU 碱基对接近。获得了开放和关闭状态的平均寿命以及转变路径时间随温度的变化。单个碱基对打开和关闭的自由能势垒源于焓的增加，这是由于碱基堆积相互作用和氢键的破坏，以及由于伴随的限制（例如扭转角约束和溶剂粘度）导致的熵损失。
