Sequence preference for BI/BII conformations in DNA: MD and crystal structure data analysis

Deciphering sequence information from sugar-phosphate backbone is finely tuned through the conformational substates of DNA. BII conformation, one of the conformational substates of B-DNA, is known to play a key role in DNA-protein recognition. BI and BII are identified by the $\epsilon-\zeta$ difference, which is negative in BI and positive in BII. Our analysis of MD and crystal structures shows that BII conformation is sequence specific and dinucleotides GC, CG, CA, TG, TA show high preference to take up BII conformation, while TT, TC, CT, CC dinucleotides rarely take up this conformation. Significant changes were observed in the dinucleotide parameters viz. twist, roll, and slide for the steps having BII conformation. Interestingly, the magnitude of variation in the dinucleotide parameters is seen to depend mainly on two factors, the magnitude of $\epsilon-\zeta$ difference and the presence or absence of BII conformation in the second strand, across the WC base-paired dinucleotide step. Based on these two factors, the conformational substate of a dinucleotide step can be further classified as BI.BI (BI conformation in both strands), BI.BII (BI conformation in one strand and BII conformation in the other), and BII.BII (BII conformation in both strands). The occurrence of BII in both strands was found to be quite rare and thus, it can be concluded that BI.BI and BI.BII hybrid steps are more favorable than a BII.BII step. In conformity with the sequence preference seen for dinucleotides in each strand, BII.BII combination of backbone conformation was observed only for GC, CG, CA, and TG containing dinucleotide steps. We further classified BII.BII step as strong BII and weak BII depending on the magnitude of the average $\epsilon-\zeta$ difference. The dinucleotide steps which belong to the category of strong BII, have large twist, high positive slide and negative roll values, while those in the weak BII group have roll, twist, and slide values similar to that of hybrid BI.BII steps. This conformational property could be contributing to the groove opening/closing and thus can modulate protein-DNA interaction