Cation-DNA outer sphere coordination in DNA polymorphism

TL;DR

This study uses molecular dynamics simulations to explore how ion coordination influences DNA conformational polymorphism in different solvent environments, revealing the role of water and methanol clusters in DNA form transitions.

Contribution

It identifies the specific ionophores responsible for A- and C-DNA forms and explains how solvent composition affects ion binding and DNA structure.

Findings

Outer sphere ion coordination influences DNA conformational states.

Water and methanol clusters modulate ion access to DNA ionophores.

Solvent environment determines DNA form transition mechanisms.

Abstract

There are two approaches to describing DNA-ions interactions. The physical approach is an analysis of electrostatic interactions between ions and charges on the DNA molecule. The coordination chemistry approach is a search for modes of direct binding of ions to ionophores of DNA. We study both the inner and outer sphere coordination of ions by ionophores of the A and C forms of DNA in molecular dynamics simulations in two low-polarity solvents: in ethanol-water and methanol-water mixtures. We show that the counterion-DNA outer sphere coordination plays a key role in the experimentally observed conformational polymorphism of the DNA molecule: a transition to the A form in ethanol and to the C form in methanol. We identify the ionophores responsible for the existence of the A- and C-complexes. In both the complexes, the ions' inner sphere ligands are mostly water molecules, the ions reside in water clusters. In ethanol-water mixture, the water clusters are large, the major groove of the A-DNA is filled with water, and all ionophores are accessible to ions. In methanol-water mixture, the water clusters are small, and a large number of methanol clusters are present near DNA surface. They interfere with the coordination of ions in one of the ionophores of the major groove, and also with other ionophores near phosphates. Therefore, in methanol, the interaction energy of counterions with A-DNA cannot compensate for the repulsion between closely located phosphates. Therefore, the ions fill more accessible ionophores of the C-complex, converting DNA into the C form.