Sequence-dependent B-A transitions in DNA in silico: Electrostatic condensation mechanism

Dynamics of the polymorphic A<->B transitions in DNA is compared for two polypurine sequences, poly(dA).poly(dT) and poly(dG).poly(dC), long known to exhibit contrasting properties in experiments. In free molecular dynamics simulations reversible transitions are induced by changing the size of a water drop around DNA neutralized by Na ions. In poly(dG).poly(dC) the B<->A transitions are easy, smooth and perfectly reversible. In contrast, a B->A transition in poly(dA).poly(dT) dodecamer fragment could not be obtained even though its A-form is stable under low hydration. Normal B->A transitions are observed, however, in long poly(dA).poly(dT) stretches flanked by GC pairs. An intermediate range of hydration numbers is identified where opposite transitions are observed in the two dodecamer fragments, namely, A->B in poly(dA).poly(dT) and B->A in poly(dG).poly(dC). With hydration numbers close to the stability limit of the B-form, the two sequences exhibit qualitatively different counterion distributions, with a characteristic accumulation of Na ions next to the opening of the minor groove in poly(dA).poly(dT). This difference can explain an increased persistence of poly(dA).poly(dT) DNA towards A-form in crystalline and amorphous fibers as compared to solution conditions. The good overall agreement with experimental data corroborates the general role of the electrostatic condensation mechanism in the A/B polymorphism in DNA.