Molecular dynamics study of the role of the spine of hydration in DNA A-tracts in determining nucleosome occupancy.

A-tracts in DNA are generally associated with reduced nucleosome occupancy relative to other sequences, such that the longer the A-tract, the less likely that nucleosomes are found. In this paper, we use molecular dynamics methods to study the structural properties of A-tracts, and in particular the role that the spine of hydration in A-tracts plays in allowing DNA to distort to the highly bent structure needed to form nucleosomes. This study includes a careful assessment of the ability of the Amber (parmbsc0), CHARMM27, and BMS force fields to describe these structural waters for the AAATTT sequence (here capped with CGC and GCG), including comparisons with X-ray results. All three force fields show a spine of hydration, but BMS and Amber show better correlation with measured properties, such as in narrowing of the minor groove width associated with the A-tract. We have used Amber to study the spine properties for several 6 and 14 base-pair A-tracts (all capped with CGC and GCG). These calculations show that the structural waters are tightly bound for "pure" A-tracts that allow for A-water-T links, and for AT steps that allow for a T-water-T link, but other sequences disfavor structural water, especially those that lead to A-water-A, G-water-G, and C-water-A structures. In addition, we show that pure A-tracts favor roll values close to the Watson-Crick value for linear DNA, while A-tract sequences containing embedded T's, C's, or G's that are less favorable to structural water are more flexible. This implies the essential role of the spine of hydration in disfavoring nucleosome formation.