Atomistic Picture of Opening-Closing Dynamics of DNA Holliday Junction Obtained by Molecular Simulations

Zhengyue Zhang, Jiří Šponer, Giovanni Bussi, Vojtěch Mlýnský, Petr Šulc, Chad R. Simmons, Nicholas Stephanopoulos, Miroslav Krepl

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)2794-2809
Number of pages16
JournalJournal of Chemical Information and Modeling
Issue number9
StatePublished - May 8 2023
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)
  • Computer Science Applications
  • Library and Information Sciences


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