DNA bending and"structural"waters in major and minor grooves of A-tracts. Monte Carlo computer simulations

To elucidate the possible role of structural waters in stabilizing bent DNA, various conformations of AT-containing decamers, (A5T5)2 and A10:T10, were studied by Monte Carlo simulations. The duplexes were constrained to reproduce the NMR inter-proton distances for the A-tracts at two temperatures: ~5° and ~35°C. Analysis of the water shell structures revealed a strong correlation between the groove widths on the one hand, and the types of hydration patterns and their probabilities on the other hand. Depending on the minor groove width, the following patterns were observed in this groove: either an interstrand "hydration spine", or interstrand two-water bridges, or a double ribbon of intrastrand sugar-base "water strings". Hydration shell in the major groove is less regular than in the minor groove, which agrees with crystallographic data. As in previous studies, energetically advantageous hydration is found for the A-tract conformations with narrow minor groove and wide major groove (B'-like DNA), known to be correlated with DNA bending and curvature. In addition, our calculations indicate that the advantage of such DNA conformations is coupled with the increase in adenine N7 hydration in the major groove. As the major groove is opened wider, its hydration shell is enriched by energetically favorable "trident waters" hydrogen bonded to three hydrophilic centers belonging to two adjacent adenines: two N7 atoms and one amino-proton H(N6). Based on these results, we suggest that formation of the novel hydration pattern in the major groove is one of the factors responsible for stabilization of the B'-like conformations of A-tracts at low temperature in the absense of dehydrating agents, leading in turn to the strong intrinsic curvature of DNA containing alternating A-tracts and "mixed" GC-rich sequences. This concept is consistent with the available experimental data, and is furthermore testable by 15N NMR.