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

0572134 - BFÚ 2024 RIV US eng J - Journal Article
Zhang, Zhengyue - Šponer, Jiří - Bussi, G. - Mlýnský, Vojtech - Sulc, P. - Simmons, Ch. R. - Stephanopoulos, N. - Krepl, Miroslav
Atomistic Picture of Opening-Closing Dynamics of DNA Holliday Junction Obtained by Molecular Simulations.
Journal of Chemical Information and Modeling. Roč. 63, č. 9 (2023), s. 2794-2809. ISSN 1549-9596. E-ISSN 1549-960X
R&D Projects: GA ČR(CZ) GA21-23718S
Institutional support: RVO:68081707
Keywords : FORCE-FIELD * BRANCH MIGRATION * NUCLEIC-ACIDS
OECD category: Inorganic and nuclear chemistry
Impact factor: 5.6, year: 2022
Method of publishing: Open access
https://pubs.acs.org/doi/10.1021/acs.jcim.3c00358

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 inter-mediates. 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.
Permanent Link: https://hdl.handle.net/11104/0349995