Positively charged ions shield the negatively charged phosphate backbone of polynucleotides allowing them to form compact intermediates. These intermediates slowly attain tertiary structures typically in the presence of divalent ions such as Mg2+ in a background of monovalent ions. To date, studies have determined specific binding sites of Mg+2 ions on RNAs, but are limited to folded conformations, such that the role of ions in RNA folding processes is still unclear. Thus, to better understand the role of metal ions in folding and stabilization of the tertiary structure of RNA we investigate the competition between monovalent and divalent ions. Here, we use a combination of umbrella sampling and oscillating chemical potential Grand Canonical Monte Carlo/Molecular Dynamics (GCMC/MD) simulations to capture the atomic-level details of the intermediate states of Twister RNA folding and characterize the distribution of ions around RNA that drive folding. The oscillating excess chemical potential allows for the sampling of Mg+2 ion distributions around partially folded states of Twister RNA. With increasing concentration of Mg2+, we observe the displacement of K+ ions by Mg2+ ions from specific binding sites. However, the monovalent ions make important contributions to folding as K+ ions interact with nucleobases and stabilize the secondary structure. Interactions of divalent ions with phosphate groups are involved in smooth transitioning from compact intermediates to tertiary structure stability. Overall, results track the ion-mediated conformational changes and establishes a better understanding of role of ions in RNA folding.

Changes in the ionic atmosphere impact the transition from compact intermediates to the folded state in Twister RNA

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.