Hydration of nucleic acid crystals.

Can we make any generalizations from examination of the crystal structures in hand? The results of study of the very well-determined high-resolution structures indicate that the counterions have a very strong effect on organizing the water structure and that these counterions are bonded in a sequence-specific manner. Hence, the sodium ion bonds in the minor groove of ApU and only to the phosphate backbone in GpC. Not surprisingly then, the water network in ApU is predominantly in its minor groove. Similarly, the negative sulfate counterion in the major groove of the 3:2 complex between proflavine and CpG has a significant influence on the water structure in that crystal. The crystallization of two positive proflavine molecules with two negative nucleic acid chains obviates the need for inorganic ions and may provide additional insight about nucleic acid water structure. The presence of the charged aromatic hydrocarbon appears to provide the correct mixture of hydrophilicity and hydrophobicity that allows for both the gathering and ordering of water molecules around the nucleic acid molecule, not unlike what was previously observed in the semiclathrate structures. This same type of hydrophobic aggregation might pertain along the major groove side of structures containing the appropriate arrangement of methyl-containing thymine bases. Although it is very tempting at this point to make further rules and predictions, experience has shown that, especially in the case of nucleic acids, such prognostications would be premature. What is clearly needed are some more high-quality crystal structures of a variety of sequences under different and controlled conditions. Analyses of these may then put us in a position to successfully predict both the structure of water and its effects on nucleic acid conformation.