Thermodynamics of site-specific small molecular ion interactions with DNA duplex: a molecular dynamics study

TL;DR

This study uses molecular dynamics simulations to analyze how small ions like Na+, TMA+, and CHO+ bind to DNA, revealing their thermodynamic preferences and the roles of entropic and enthalpic factors in stabilization.

Contribution

It provides detailed atomistic insights into the site-specific binding and thermodynamic contributions of different small ions to DNA stability, which was not previously characterized.

Findings

All ions preferentially bind to the DNA minor groove.

Binding is entropically driven for all ions.

Hydrophobic effects and hydrogen bonding influence stabilization.

Abstract

The stability and dynamics of a double-stranded DNA (dsDNA) is affected by the preferential occupancy of small monovalent molecular ions. Small metal and molecular ions such as sodium and alkyl ammonium have crucial biological functions in human body, affect the thermodynamic stability of the duplex DNA and exhibit preferential binding. Here, using atomistic molecular dynamics simulations we investigate the preferential binding of metal ion such as Na+ and molecular ions such as tetramethyl ammonium (TMA+) and 2-hydroxy-N,N,N-trimethylethanaminium (CHO+) to double stranded DNA. The thermodynamic driving force for a particular molecular ion- DNA interaction is determined by decomposing the free energy of binding into its entropic and enthalpic contributions. Our simulations show that each of these molecular ions preferentially binds to the minor groove of the DNA and the extent of binding is highest for CHO+. The ion binding processes are found to be entropically favourable. In addition, the contribution of hydrophobic effects towards the entropic stabilization (in case of TMA+) and the effect of hydrogen bonding contributing to enthalpic stabilization (in case of CHO+) have also been investigated.