A base-sugar-phosphate three-layer ONIOM model for cation binding: Relative binding affinities of alkali metal ions for phosphate anion in DNA

Abstract

A three layer ONIOM approach was used to study the interactions of hydrated alkali metal ions such as Li+, Na+, and K+ with a DNA fragment containing two phosphate groups, three sugar units, and a G center dot center dot C base pair modeled in the anion and dianion states. Among the three metal- binding combinations studied herein (outer- sphere, inner- sphere monodentate, and inner- sphere bidentate), the outer- sphere binding mode showed the highest binding energy (BE) for hydrated Li+ ions (103.1 kcal/ mol) while the hydrated Na+ and K+ ions preferred the inner-sphere monodentate binding modes to the phosphate group of the anionic DNA fragment (BE) 87.9 and 98.2 kcal/ mol for Na+ and K+, respectively). These data on the binding mechanisms of Li+, Na+, and K+ ions and the higher binding affinity of Li+ ions compared to Na+ and K+ ions in the anion model system of DNA are in good agreement with the previous experimental findings. On the other hand, in the dianion state, Li+ preferred inner- sphere monodentate, whereas Na+ and K+ ions preferred the outer- sphere structures. The neutral anion model ion revealed a more realistic picture of DNA- alkali metal ion interactions compared to the non- neutral dianion model systems