Influence of Na+ and Mg2+ ions on RNA structures studied with molecular dynamics simulations

Abstract

The structure of ribonucleic acid (RNA) polymers is strongly dependent on the presence of, in particular Mg2+ cations to stabilize structural features. Only in high-resolution X-ray crystallography structures can ions be identified reliably. Here, we perform molecular dynamics simulations of 24 RNA structures with varying ion concentrations. Twelve of the structures were helical and the others complex folded. The aim of the study is to predict ion positions but also to evaluate the impact of different types of ions (Na+ or Mg2+) and the ionic strength on structural stability and variations of RNA. As a general conclusion Mg2+ is found to conserve the experimental structure better than Na+ and, where experimental ion positions are available, they can be reproduced with reasonable accuracy. If a large surplus of ions is present the added electrostatic screening makes prediction of binding-sites less reproducible. Distinct differences in ion-binding between helical and complex folded structures are found. The strength of binding (ΔG‡ for breaking RNA atom-ion interactions) is found to differ between roughly 10 and 26 kJ/mol for the different RNA atoms. Differences in stability between helical and complex folded structures and of the influence of metal ions on either are discussed.

Quantitative studies of an RNA duplex electrostatics by ion counting

“…E.g., monovalent cation occupancy in the dsDNA and dsRNA ion atmosphere is insensitive to the cation size across the alkali metal ions Na + , K + , Rb + , and Cs + , contrary to all-atom computational models and highlighting the need to reevaluate molecular mechanical force fields for solute-solvent and solventsolvent interactions. Our new experimental results for dsRNA-ion interactions provide the opportunity to test newly developed all-atom models of RNA-Mg 2+ interactions (70,72,74,76,77) and initiate a feedback loop between computation and experiment.…”

“…Experimental methods like ion counting can quantify the overall content of the ion atmosphere and energetics of competitive association of cations but does not provide information about the distribution of ions within the atmosphere. Computational models can in principle provide a thorough and deep understanding of ion-nucleic acid interactions, solvent-nucleic acid interactions, and the dynamic and energetic consequences of these interactions(31,35,60,(68)(69)(70)(71)(72)(73)(74)(75). However, the accuracy of such models cannot be assumed, and even matching to one a few prior experimental measurements in insufficient to establish the veracity of models for systems as complex and multi-variant as nucleic acid/ion interactions in solution.…”

Gas‐phase hydration of Mg2+ complexes with deprotonated uracil, thymine, uridine, and thymidine

“…One of the most important biological roles of Mg 2+ cation is related to its interactions with nucleic acids, both DNA and RNA. For example, Mg 2+ may play a catalyst role in self‐cleaving ribozymes, it is necessary for proper activities of deoxyribozymes, it stabilizes the RNA tertiary structure, and Mg 2+ ‐nucleic acids interactions are of importance in a number of other phenomena …”

Surviving the deluge of biosimulation data

“…This encourages the study of complex ultra‐flexible systems such as intrinsically disordered proteins or unpaired nucleic acids. Despite their known limitations, improvements in the current generation of force fields offer researchers increasingly refined tools to investigate the behavior of complex biomacromolecules The improvements in the simulation engines .…”