Mg(H2O)62+-?(cytosine) interactions in a DNA dodecamer

Abstract

In a recent investigation we performed extensive Monte Carlo calculations on the sequence-specific binding of hydrated magnesium ions to DNA. One of the DNA models considered used coordinates from a high-resolution crystal structure of the dodecamer duplex d(CGCGAATTCGCG)2 in which a hydrated magnesium ion is outer-sphere-coordinated to the dodecamer. In analogy with cation–π interactions in proteins, it has been suggested that the local base unstacking observed in this structure is due to similar interactions between cytosine rings and a nearby magnesium ion. As our (and most) Monte Carlo and molecular dynamics simulations of cation–DNA interactions rely only on the electrostatic and Lennard–Jones (6–12) components of standard force fields to describe such situations, we undertook a detailed ab initio study of selected cation–π interactions in this crystal structure to gauge their strength. The results of this investigation involving the 6-31G*, 6-31+G*, and 6-311++G** basis sets at the restricted Hartree–Fock, Møller–Plesset second-order perturbation and density functional levels are presented here within the context of previous cation–π studies. We find that, for this particular crystal structure, the average binding energy between the hydrated magnesium ion and one of the three nearest cytosine bases is about −1.8±1.0 kcal/mol. We therefore rule out these specific cation–π interactions between a hydrated magnesium ion and cytosine rings as the cause of the observed base unstacking. © 2002 John Wiley & Sons, Inc. Int J Quantum Chem, 2002