Book of Abstracts: Albany 2005
Electrostatic Polymer Condensation and the A/B Polymorphism in DNA
Stable dynamics of A-DNA and reversible B↔A transitions can be studied in MD simulations with vacuum boundaries. In this approach, a DNA fragment is placed in a water drop and neutralized with free ions. The drop size is maintained during simulations by periodical artificial return of the evaporated water molecules. The relative stability of A and B forms is modulated by changing the size of the drop, with spontaneous transitions observed in both directions and reversed, if necessary. The major driving force of the B→A transition comes from accumulation of free metal cations in the opening of the major groove that results in inversion of electrostatic interactions between the phosphates of opposite backbone strands. This transition, therefore, is similar to the well known phenomenon of free-ion-mediated electrostatic condensation of polyelectrolytes, but here it occurs inside the DNA duplex. With certain assumptions, this mechanism can be applied to experimental B↔A transitions, notably, it offers a detailed interpretation of the long known cooperative effects. The critical transition hydration is close to experiment without any additional fitting of the forcefield, suggesting that the physics of the transitions is reasonably well reproduced. The well documented experimental resistance of poly(dA)·poly(dT) duplex to the B→A transition has been recovered in simulations and shown to be caused by thymine methyl groups. With several duplexes placed in the same drop, we obtain new insights in B↔A transitions in DNA fibers.
References and Footnotes
Alexey K. Mazur
Laboratoire de Biochimie Theorique