Book of Abstracts: Albany 2011

category image Albany 2011
Conversation 17
June 14-18 2011
©Adenine Press (2010)

Molecular Dynamics Simulations of DNA Holliday Junctions: Conformational Stability and Transitions

Holliday Junctions (4W-junctions) are highly conserved four-way DNA homologous replication junctions capable of undergoing salt-dependent conformational transitions between mobile open planar and immobile stacked-X forms (1). This study investigates the effect of salt concentration on Holliday Junction conformation and dynamics. All-atom Molecular Dynamics (MD) simulations are reported on 17 base-pair Holliday Junctions with "Junction 3" (J3) cores (2). We carried out the calculations in different ionic concentrations to facilitate the transition between open and stacked-X conformers. The results were analyzed in terms of free energy landscapes obtained with Principal Component Analysis. In low salt conditions (electroneutrality), the open planar form transitioned to the lesser-observed Iso I stacked-X form by passing through a tetrahedral intermediate species capable, in theory, of adopting several stacked conformations (3). The higher salt condition (70mM KCl) revealed a transition from open to the experimentally observed Iso II stacked form without the presence of an intermediate species. A free energy map of the lower salt condition reveals a multistate model with three distinct minima, two for the open/stacked-X conformations, and a third accounting for the tetrahedral intermediate state. On the other hand, a free energy map of the high salt simulation reveals a distinctly two-state model with two minima and a narrow pathway (energy barrier) connecting the two. The findings imply that there is a unique stacking pathway along the free energy surface for the J3 4W-junction in a high salt condition where phosphate charges are adequately shielded.

Above: Holliday Junction open and stacked forms


  1. F. Hays, J. Watson, and P. Ho, J.B.C. 278, 49663-49666 (2003).
  2. D. R. Duckett, A. Murchie, S. Diekmann, E. Kitzing, B. Kemper, and D. Lilley, Cell 58, 79-89 (1988).
  3. J. Yu, T. Ha, and K. Schulten, NAR 32, 6683-6695 (2004).

Elizabeth G. Wheatley
Susan Pieniazek
David L. Beveridge

Department of Chemistry
Wesleyan University
Middletown, CT 06459

Ph: (860) 685-3543
Fx: (860) 685-2211