Influence of the dynamic positions of cations on the structure of the DNA minor groove: Sequence-dependent effects

Different models for minor groove structures predict that the conformation is essentially fixed by sequence and has an influence on local ion distribu tion or alternatively that temporal positions of ions around the minor groo ve can affect the structure if they neutralize cross-strand phosphate charg es. Our previous studies show that the minor groove in an AATT dodecamer re sponds to local sodium ion positions and is narrow when ions neutralize cro ss-strand phosphate-phosphate charges [J. Am. Chem. Soc. 2000, 122, 10513-1 0520]. Previous results from a number of laboratories have shown that G-tra cts often have a wider minor groove than A-tracts, but they do not indicate whether this is due to reduced flexibility or differences in ion interacti ons. We have undertaken a molecular dynamics study of a d(TATAGGCCTATA) dup lex to answer this question. The results show that the G-tract has the same amplitude of minor groove fluctuations as the A-tract sequence but that it has fewer ion interactions that neutralize cross-strand phosphate charges. These results demonstrate that differences in time-average groove width be tween A- and G-tracts are due to differences in ion interactions at the min or groove. When ions neutralize the cross-strand phosphates, the minor groo ve is narrow. When there are no neutralizing ion interactions, the minor gr oove is wide. The population of structures with no ion interactions is larg er with the GGCC than with the AATT duplex, and GGCC has a wider time-avera ge minor groove in agreement with experiment.