The role of electrostatics in the B to A transition of DNA: from solution to assembly

On the basis of a wealth of published experimental data and computer simulations, we build a simple physical model that allows us to rationalize the A to B transition of DNA in solution and in aggregates. In both cases we find that the electrostatic interactions are strong enough, alone, to induce the transition independently of other energetic contributions, e. g. those related to hydration. On the basis of this analysis we conclude that in ethanol/water mixtures, the effect responsible for the transition is the reduction of dielectric constant in the mixture. This is manifested in electrostatic self-energy terms that include the interaction of phosphate charges with condensed counterions. But in dense aggregates, electrostatics plays a dual role, giving rise to two competing effects. In the absence of groove localized counterions the electrostatic self-energy favours the B form, and the electrostatic interaction energy between neighbouring DNA favours the A form. However, the addition of enough counterions localized in the narrow groove reverses this. In dry aggregates of DNA both terms, in most cases, conspire to keep DNA in the A form. The analysis gives a broad picture of the B to A transition and sets a number of new research goals, particularly concerning simulations that may test our simple model for aggregates.