Flexible structure of DNA: Ion dependence of minor-groove structure and dynamics

The structure and dynamics of the grooves of DNA are of immense importance for recognition of DNA by proteins and small molecules as well as for the packaging of DNA into nucleosomes and viral particles. Although there is general agreement that the minor groove of DNA varies in a sequence-dependent manner and is narrow in AT regions, alternative models have been presented to explain the molecular basis for the groove narrowing. In one model the groove narrowing results from direct, short-range interactions among DNA bases. In this model the minor groove width of a given sequence is fixed, and any localization of monovalent cations in the groove does not affect the groove structure. In an alternative model the narrow minor groove of A-tracts is proposed to originate from sequence-dependent localization of water and cations. Ion dynamics and exchange make experimental tests of these models difficult, but they can be directly tested by determining how DNA minor-groove structure responds to cation positions in the course of molecular dynamics (MD) simulations. To carry out such a test, we have conducted a long MD simulation on the sequence d(CGCGAATTCGCG)(2) in the presence of ions and water. We have analyzed the major structures that exist and the correlation between ion population and minor groove width. The results clearly show a time-dependent influence of ion positions on minor groove structure. When no ions interact with the groove, the groove is wide. Ion-water interactions narrow the groove through two distinct interactions: (i) ions interact directly with the DNA bases in the minor groove, such as cross-strand thymine oxygens (O2) in the sequence above, to give an internal ion-spine of hydration, or (ii) ions interact with phosphate groups in the AT sequence while water molecules in the minor groove interact directly with the bases. Some variations on these limiting models are possible in a dynamic DNA-water-ion structure, but it is clear that ion and water interactions at AT base pair sequence sites are required to yield the observed narrow minor groove in AT sequences.