Sequence-dependent B <-> A transition in DNA evaluated with dimeric and trimeric scales

Experimental data on the sequence-dependent B-A conformational transition i n 24 oligo- and polymeric duplexes yield optimal dimeric and trimeric scale s for this transition. The 10 sequence dimers and the 32 trimers of the DNA duplex were characterized by the free energy differences between the B and A forms in water solution. In general, the trimeric scale describes the se quence-dependent DNA conformational propensities more accurately than the d imeric scale, which is likely related to the trimeric model accounting for the two interfaces between adjacent base pairs on both sides (rather than o nly one interface in the dimeric model). The exceptional preference of the B form for the AA:TT dimers and AAN:NTT trimers is consistent with the coop erative interactions in both grooves. In the minor groove, this is the hydr ation spine that stabilizes adenine runs in B form. In the major groove, th ese are hydrophobic interactions between the thymine methyls and the sugar methylene groups from the preceding nucleotides, occurring in B form. This interpretation is in accord with the key role played by hydration in the B- A transition in DNA. Importantly, our trimeric scale is consistent with the relative occurrences of the DNA trimers in A form in protein-DNA cocrystal s. Thus, we suggest that the B/A scales developed here can be used for anal yzing genome sequences in search for A-philic motifs, putatively operative in the protein-DNA recognition.