Atomistic Landscape of Opening-Closing Dynamics of DNA Holliday Junction Obtained by Molecular Simulations
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| Year of publication | 2023 |
| Type | Conference abstract |
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| Description | Holliday Junction (HJ) is a non-canonical four-way DNA structure with a prominent role in DNA repair, recombination and DNA nanotechnology. By rearranging its four arms, HJ can adopt either a closed or open state. With enzymes typically recognizing only a single state, acquiring detailed knowledge of the rearrangement process is an important step towards fully understanding the biological function of HJs. Here, we carried out standard all-atom molecular dynamics (MD) simulations of the spontaneous openingclosing transitions, which revealed complex conformational transitions of HJs with the involvement of previously unconsidered “half-closed” intermediates. Detailed free-energy landscapes of the transitions were obtained by sophisticated enhanced sampling simulations, which also reproduced the ionic strength dependence of the HJ dynamics. Because the force field overstabilizes the closed conformation of HJs, we developed a system-specific force field modification which weakens the Lennard-Jones interactions of the branch point nucleotides. Our methods allow for the firsttime observation of spontaneous opening-closing HJ transitions in unbiased MD simulations and open possibilities for more accurate HJ computational studies of biological processes and nanomaterials. |
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