Comparison of major groove hydration in isomorphous A-DNA octamers and dependence on base sequence and local helix geometry.

The family of ten isomorphous tetragonal A-DNA octamers provides a unique opportunity to examine major groove hydration in terms of base sequence and local parameter effects. The presence of a severely underwound central py.pu base step (average = 24.1 degrees), which lies on a crystallographic 2-fold in the unit cell, provides a sharp change in the local environment in which to study and separate the effects of base sequence and local helix geometry on major groove hydration. For this reason, and to avoid bias secondary to end effects, hydration analysis was restricted to the central four dyad-related base paris. This study finds that d(CG) base pairs are better hydrated than d(TA) base pairs, 2.5 H2O vs 1.3 H2O; steps with high twist angles are better hydrated than steps with low twist angles, 6.9 H2O vs 0 H2O; negative roll angles are better hydrated than positive roll angles, 2.8 H2O vs 1.8 H2O; and flanking base pairs are better hydrated than central base pairs, 2.6 H2O vs 2.0 H2O, a phenomenon which is sequence independent, occurring for both d(CG) and d(TA) base pairs. The twist angle and base roll combine to significantly affect the pattern and degree of major groove hydration in this family of octamers. A previous study of A-DNA octamers and their helix parameters established a strong dependency on crystal packing forces with little or no dependence on the base sequence [Ramakrishnan & Sundaralingam (1993) J. Biomol. Struct. Dyn. 11. 11-26]. We find that the degree and pattern of major groove hydration are strongly influenced by the local helix parameters, implying an indirect, but significant, relationship between major groove hydration and environmental forces, i.e., crystal packing, drug binding, and protein-DNA interactions.