Multivalent ion-mediated nucleic acid helix-helix interactions: RNA versus DNA

TL;DR

This study uses atomistic molecular dynamics to compare how multivalent ions mediate interactions between RNA and DNA helices, revealing different binding modes and conditions for attraction or repulsion.

Contribution

It provides detailed atomistic insights into ion-mediated nucleic acid interactions, highlighting differences between RNA and DNA helix topologies and ion binding behaviors.

Findings

B-DNA exhibits strong attraction at high Co-Hex concentration.

A-RNA remains weakly repulsive unless in specific conditions.

Deep major grooves influence ion binding and helix interactions.

Abstract

Ion-mediated interaction is critical to the structure and stability of nucleic acids. Recent experiments suggest that the multivalent ion-induced aggregation of double-stranded (ds) RNAs and DNAs may strongly depend on the topological nature of helices, while there is still lack of an understanding on the relevant ion-mediated interactions at atomistic level. In this work, we have directly calculated the potentials of mean force (PMF) between two dsRNAs and between two dsDNAs in Cobalt Hexammine ion (Co-Hex) solutions by the atomistic molecular dynamics simulations. Our calculations show that at low [Co-Hex], the PMFs between B-DNAs and between A-RNAs are both (strongly) repulsive.However, at high [Co-Hex], the PMF between B-DNAs is strongly attractive, while those between A-RNAs and between A-DNAs are still (weakly) repulsive. The microscopic analyses show that for A-form helices, Co-Hex would become internal binding into the deep major groove and consequently cannot form the evident ion-bridge between adjacent helices, while for B-form helices without deep grooves, Co-Hex would exhibit external binding to strongly bridge adjacent helices. In addition, our further calculations show that, the PMF between A-RNAs could become strongly attractive either at very high [Co-Hex] or when the bottom of deep major groove is fixed with a layer of water.