Unraveling the sequence-dependent polymorphic behavior of d(CpG) steps

We have made a detailed study of one of the most surprising sources of polymorphism in B-DNA: the high twist/low twist (HT/LT) conformational change in the d(CpG) base pair step. Using extensive com-putations, complemented with database analysis, we were able to characterize the twist polymorphism in the d(CpG) step in all the possible tetranucleotide en-vironment. We found that twist polymorphism is cou-pled with BI/BII transitions, and, quite surprisingly, with slide polymorphism in the neighboring step. Un-expectedly, the penetration of cations into the mi-nor groove of the d(CpG) step seems to be the key element in promoting twist transitions. The tetranu-cleotide environment also plays an important role in the sequence-dependent d(CpG) polymorphism. In this connection, we have detected a previously un-explored intramolecular C-H···O hydrogen bond in-teraction that stabilizes the low twist state when 3′-purines flank the d(CpG) step. This work explains a coupled mechanism involving several apparently un-correlated conformational transitions that has only been partially inferred by earlier experimental or the-oretical studies. Our results provide a complete de-scription of twist polymorphism in d(CpG) steps and a detailed picture of the molecular choreography as-sociated with this conformational change