TY - JOUR
T1 - Atomistic Picture of Opening-Closing Dynamics of DNA Holliday Junction Obtained by Molecular Simulations
AU - Zhang, Zhengyue
AU - Šponer, Jiří
AU - Bussi, Giovanni
AU - Mlýnský, Vojtěch
AU - Šulc, Petr
AU - Simmons, Chad R.
AU - Stephanopoulos, Nicholas
AU - Krepl, Miroslav
N1 - Funding Information:
This work was supported by the Czech Science Foundation (21-23718S) (Z.Z., J.S., V.M., M.K.) and by the H2020-MSCA-ITN project 765266 (LightDyNAmics) by European Commission (Z.Z.).
Publisher Copyright:
© 2023 The Authors. Published by American Chemical Society.
PY - 2023/5/8
Y1 - 2023/5/8
N2 - 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.
AB - 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.
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U2 - 10.1021/acs.jcim.3c00358
DO - 10.1021/acs.jcim.3c00358
M3 - Article
C2 - 37126365
AN - SCOPUS:85156230843
SN - 1549-9596
VL - 63
SP - 2794
EP - 2809
JO - Journal of Chemical Information and Modeling
JF - Journal of Chemical Information and Modeling
IS - 9
ER -