Electrostatic Polymer Condensation and the A/B Polymorphism in DNA:  Sequence Effects

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 sodium ions. In poly(dG).poly(dC) the B↔A transitions are easy, smooth and perfectly reversible. In contrast, a B→A transition in a poly(dA).poly(dT) dodecamer fragment could not be obtained even though its A-form is stable under low hydration. An intermediate range of hydration numbers is identified where opposite transitions are observed, namely, A→B in poly(dA).poly(dT) and B→A in poly(dG).poly(dC). The two sequences exhibit qualitatively different counterion distributions, with a characteristic accumulation of sodium in the major groove of poly(dG).poly(dC) and the B→A transition driven by the electrostatic condensation mechanism. The resistance of the poly(dA).poly(dT) sequence to adopting the A-form is traced to the specific steric interactions of thymine methyl groups in the major groove. With these methyls replaced by hydrogens, reversible B↔A transitions become possible and the difference between the two molecules is significantly reduced. The good overall agreement with experimental data corroborates the general role of the electrostatic condensation mechanism in the A/B polymorphism in DNA.