A base-centred explanation of the B-to-A transition in DNA

In the traditional view, the bistable feature responsible for the switch between the B and A forms of DNA was the sugar-phosphate backbone. Several recent assays of the sequence-dependent structure of DNA are not compatible with that hypothesis. Here we show that certain kinds of base-pair step, mainly those of the pyrimidine-purine variety, can stack in a “bistable” fashion so as to produce one of two overall helix shapes A or B. Further, we suggest that the passive, elastic stiffness of the backbone is responsible for communicating the stacking configuration from bistable steps to their “neutral” neighbours. The role of water molecules, in stabilizing the B form of DNA over the A, may simply be to form hydrogen-bonded bridges with the minor-groove edges of neutral steps in the B configuration.