Mg2+ ions are fundamental in RNA biology playing a crucial role in screening the highly negative charge of the sugar-phosphate backbone, regulating the folding process and acting as cofactors in several reactions involving RNA filaments. In this context, the integrative support of atomistic simulations can contribute to better decipher Mg2+/RNA interplay. Yet, the available force fields (FF) are plagued by inaccuracies and intrinsically neglect the different electronic effects that Mg2+ ion exerts in varying RNA coordination environments. Here, we have performed a computational study combining classical molecular dynamics (MD) and Density Functional Theory (DFT) calculations aimed at characterizing the performance of five Mg2+ FF models in two prototypical Mg2+-dependent ribozymes. We have also enlightened how charge transfer and polarization affect the binding of Mg2+ ions in different coordination motifs. Our MD simulations unveiled remarkable differences in terms of populations of coordination sites accounted by the five Mg2+ FFs and responsiveness to a change of Mg2+ concentration. Moreover, complementary DFT calculations disclosed that electronic properties of Mg2+ ion such as charge transfer and polarization effects remain constant in varying Mg2+-RNA coordination motifs. Overall, our study constitutes a guideline for an adept use of current Mg2+ models and provides novel insights for the rational development of next-generation Mg2+ FFs to be employed for atomistic simulations of RNA.

Structural and electronic features of Mg2+-RNA binding motifs: Insights from combined classical molecular dynamics and quantum mechanics simulations

253rd National Meeting (2017)

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