Molecular simulation study of RNA/dopamine complex dynamics at varying concentrations

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.