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

Area of Science:

• Biophysics
• Molecular Biology
• Computational Chemistry

Background:

• Ion-mediated interactions are crucial for nucleic acid structure and stability.
• Multivalent ion-induced aggregation of double-stranded (ds) RNA and DNA is sensitive to helix topology.
• Atomistic understanding of these ion-mediated interactions is lacking.

Purpose of the Study:

• To investigate ion-mediated interactions between nucleic acids at the atomistic level.
• To elucidate the role of helix topology in multivalent ion-induced aggregation.
• To compare the binding mechanisms of Cobalt Hexammine (Co-Hex) with B-DNA and A-RNA/DNA.

Main Methods:

• Atomistic molecular dynamics simulations.
• Calculation of potentials of mean force (PMF).
• Analysis of ion binding sites and interactions.

Main Results:

• At low Co-Hex concentrations, PMFs between B-DNA and A-RNA are repulsive.
• At high Co-Hex concentrations, B-DNA exhibits strong attraction, while A-RNA and A-DNA remain weakly repulsive.
• Co-Hex shows 'internal binding' in A-form helices' major groove, preventing inter-helix bridging, versus 'external binding' in B-form helices, facilitating bridging.

Conclusions:

• The topological difference between A-form and B-form helices dictates distinct multivalent ion binding modes.
• This difference in binding mode explains the varying aggregation behaviors of dsRNA and dsDNA in Co-Hex solutions.
• A-RNA aggregation can become attractive at extremely high Co-Hex concentrations or with specific groove modifications.