Holliday junction (HJ) is a noncanonical four-way DNA
structure
with a prominent role in DNA repair, recombination, and DNA nanotechnology.
By rearranging its four arms, HJ can adopt either closed or open state.
With enzymes typically recognizing only a single state, acquiring
detailed knowledge of the rearrangement process is an important step
toward fully understanding the biological function of HJs. Here, we
carried out standard all-atom molecular dynamics (MD) simulations
of the spontaneous opening–closing transitions, which revealed
complex conformational transitions of HJs with an involvement of previously
unconsidered “half-closed” intermediates. Detailed free-energy
landscapes of the transitions were obtained by sophisticated enhanced
sampling simulations. Because the force field overstabilizes the closed
conformation of HJs, we developed a system-specific modification which
for the first time allows the observation of spontaneous opening–closing
HJ transitions in unbiased MD simulations and opens the possibilities
for more accurate HJ computational studies of biological processes
and nanomaterials.