NEW INSIGHTS INTO THE STRUCTURE OF AN TRACTS AND B'-B' BENDS IN DNA

Energy calculations suggest that the currently available NOE distance constraints for A(n) tracts in DNA are incapable of distinguishing between structures with a narrowed minor groove arising from a large propeller twist with a small inclination or from a small propeller twist with a large negative inclination. Furthermore, analysis of published data, together with energy estimations, strongly argue against bifurcated hydrogen bonding between A and T residues being the cause of the anomalous structural properties of A(n) tracts. A conformational analysis of the B'-B' junction has been performed in which a single variable base pair has been inserted between two regions of B' structure. We have calculated low-energy structures for A(n)GA(n), A(n)CA(n), A(n)TA(n), A(n)CT(n), and T(n)CA(n) duplexes, where the A(n) and T(n) tracts were fixed in the anomalous B' conformation. Upon optimization, all these structures were found to contain a pronounced roll-like bending into the major groove at the site of the insertion. The important factors in the formation of these B'-B' bends are the destruction of the B' conformation and the concomitant widening of the minor groove at the junction region in order to reduce minor groove interstrand base clashes and improve interstrand stacking energy. If the B' conformation has strong negative inclination, the improved intrastrand stacking energy also contributes to the bending. In calculations of duplexes with A(n) and T(n) tracts in the B conformation instead of B', the bending disappears.