Poghosyan Armen H, Mamasakhlisov Yevgeni S, Parsadanyan Marine A, Shahinyan Mariam A, Movsisyan Zvart H, Vardevanyan Poghos O
Laboratory of Bioinformatics, Institute of Informatics and Automaton Problems of NAS RA, P. Sevak 1, 0014, Yerevan, Armenia.
Institute of Applied Problem of Physics, H. Nersisyan 25, 0014, Yerevan, Armenia.
Sci Rep. 2025 Jul 1;15(1):21379. doi: 10.1038/s41598-025-06690-7.
The interaction between dopamine and RNA structures holds significant potential for understanding neurotransmitter-driven RNA modulation and biosensor design. Here, we employ all-atom molecular dynamics (MD) simulations to investigate the concentration-dependent binding of dopamine to poly(rA)/poly(rU) complex. We reveal that the dopamine molecules are preferentially trapped by poly(A)/poly(U) complex where the dopamine catechol rings became oriented parallel towards to RNA amine rings, although with the increase of dopamine concentration we track a multi-mode binding of dopamine molecules, i.e., different configurations can be found. The increasing of dopamine concentration leads to the dense packing of poly(A)/poly(U) complex, where more than half of dopamine molecules are strongly bound. We argue that the dopamine shows mainly intercalation mechanism of stabilization of poly(A)-poly(U) complexes governed by the hydrogen bonds network formation. These findings offer new insights relevant to RNA-based biosensors and the interplay between neurotransmitters and nucleic acids.
多巴胺与RNA结构之间的相互作用在理解神经递质驱动的RNA调节和生物传感器设计方面具有巨大潜力。在此，我们采用全原子分子动力学（MD）模拟来研究多巴胺与聚（rA）/聚（rU）复合物的浓度依赖性结合。我们发现多巴胺分子优先被聚（A）/聚（U）复合物捕获，其中多巴胺儿茶酚环朝着RNA胺环平行排列，尽管随着多巴胺浓度的增加，我们追踪到多巴胺分子的多模式结合，即可以发现不同的构型。多巴胺浓度的增加导致聚（A）/聚（U）复合物紧密堆积，其中超过一半的多巴胺分子强烈结合。我们认为多巴胺主要通过氢键网络形成表现出稳定聚（A）-聚（U）复合物的嵌入机制。这些发现为基于RNA的生物传感器以及神经递质与核酸之间的相互作用提供了新的见解。
