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Peer-reviewedCC BY 4.0International Journal of Molecular Sciences

Molecular Dynamics Simulations Reveal a Broadly Open Solution Ensemble for the DNA Holliday Junction: Mg2+ Crossover Bridging and Weak Force-Field Sensitivity

  • Yonghui Zhang1,2
  • Yujia Zhou3,4,5
5 affiliations
  1. 1Institute of Computing Science and Technology, Guangzhou University, Guangzhou 510006, China
  2. 2Huangpu Research School, Guangzhou University, Guangzhou 510006, China
  3. 3School of Biomedical Engineering, Southern Medical University, Guangzhou 510515, China
  4. 4Guangdong Provincial Key Laboratory of Medical Image Processing, Southern Medical University, Guangzhou 510515, China
  5. 5Guangdong Provincial Engineering Laboratory for Medical Imaging and Diagnostic Technology, Southern Medical University, Guangzhou 510515, China
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Abstract

Holliday junctions, four-way DNA crossovers central to DNA origami and key intermediates of homologous recombination, must be accurately modeled for rational DNA-nanodevice design, yet their solution conformational ensemble remains incompletely characterized. We characterize this ensemble for the experimental junction d(TCGGTACCGA)4 by all-atom molecular dynamics, comparing the AMBER force fields parmbsc1, OL21, and OL24 in OPC water with matched ionic conditions. In every force field, the junction explores a broad, nearly flat inter-arm-angle landscape, with <1 kcal/mol variation across inter-arm angles of 2–90°: the open state is favored by 0.45–0.63 kcal/mol, the crystallographic-like inter-arm angle occurs in 2–5% of frames, and the crossover remains coaxially stacked whether open or compact. A Mg2+ ion occupies the crossover pocket in 92–94% of frames, specifically bridging the A- and C-strand phosphates (Li–Merz CM Mg2+ set). Stacking-isomer exchange between the A/C-continuous and crystallographic B/D isomers proceeds at ~0.5 ns−1 in this minimal short-arm construct, independent of force field, with A/C-continuous favored ~2:1. parmbsc1 yields a more open junction than OL21 and OL24, which reproduce the crystallographic inter-arm angle of 39–43°; the sugar-pucker shift targeted in OL24 is also visible at the junction. These results establish a force-field-robust baseline for simulation-guided design of crossover-containing nanostructures.

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Cite

BibTeXRIS
BibTeX
@article{zhang2026molecular,
  title = {{Molecular Dynamics Simulations Reveal a Broadly Open Solution Ensemble for the DNA Holliday Junction: Mg2+ Crossover Bridging and Weak Force-Field Sensitivity}},
  author = {Yonghui Zhang and Yujia Zhou},
  journal = {International Journal of Molecular Sciences},
  year = {2026},
  month = oct,
  doi = {10.3390/ijms27219634},
  url = {https://www.mdpi.com/1422-0067/27/21/9634},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Molecular Dynamics Simulations Reveal a Broadly Open Solution Ensemble for the DNA Holliday Junction: Mg2+ Crossover Bridging and Weak Force-Field Sensitivity
AU  - Yonghui Zhang
AU  - Yujia Zhou
PY  - 2026
DA  - 2026/10/28
JO  - International Journal of Molecular Sciences
DO  - 10.3390/ijms27219634
UR  - https://www.mdpi.com/1422-0067/27/21/9634
AB  - Holliday junctions, four-way DNA crossovers central to DNA origami and key intermediates of homologous recombination, must be accurately modeled for rational DNA-nanodevice design, yet their solution conformational ensemble remains incompletely characterized. We characterize this ensemble for the experimental junction d(TCGGTACCGA)4 by all-atom molecular dynamics, comparing the AMBER force fields parmbsc1, OL21, and OL24 in OPC water with matched ionic conditions. In every force field, the junction explores a broad, nearly flat inter-arm-angle landscape, with <1 kcal/mol variation across inter-arm angles of 2–90°: the open state is favored by 0.45–0.63 kcal/mol, the crystallographic-like inter-arm angle occurs in 2–5% of frames, and the crossover remains coaxially stacked whether open or compact. A Mg2+ ion occupies the crossover pocket in 92–94% of frames, specifically bridging the A- and C-strand phosphates (Li–Merz CM Mg2+ set). Stacking-isomer exchange between the A/C-continuous and crystallographic B/D isomers proceeds at ~0.5 ns−1 in this minimal short-arm construct, independent of force field, with A/C-continuous favored ~2:1. parmbsc1 yields a more open junction than OL21 and OL24, which reproduce the crystallographic inter-arm angle of 39–43°; the sugar-pucker shift targeted in OL24 is also visible at the junction. These results establish a force-field-robust baseline for simulation-guided design of crossover-containing nanostructures.
SN  - 1422-0067
ER  -