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Peer-reviewedCC BY 4.0Biomolecules

Mechanical Rupture of DNA Tension-Gate Elements: Thresholds, Kinetics, and Energetics from Steered Molecular Dynamics

  • 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

The kinetics and energetics of load-driven conformational rearrangements underlie DNA replication, repair, and DNA nanodevice function. DNA tension-gate tethers exploit these dynamics, yet their rupture thresholds are set almost exclusively by single-molecule calibration; here, an atomistic steered-molecular-dynamics pipeline predicts relative thresholds and characterizes the underlying rearrangements. Seven constructs—duplexes of varying length and GC content, single-stranded poly(dT)30, a GC-clamped hairpin, and G-quadruplex—were pulled with 50 trajectories per construct per rate (0.01/0.001 nm/ps). At MD loading rates, the ordering G-quadruplex (911 pN) > GC-rich duplex (786 pN) > hairpin (643 pN) > mixed duplexes (559/558 pN) > ssDNA (388 pN) holds at both rates, and the design rules deconfound, +68 pN for GC content (47% → 100%), −160 pN for doubled length, and 208 pN for pull geometry—larger than GC itself. Dissipated work falls 31–58% at the slower rate; slow-rate Jarzynski estimators converge for low-dissipation elements, while fast-rate profiles of high-dissipation motifs do not. Absolute thresholds at experimental rates remain out of reach, but the ordering—the actionable output for TGT design—comes with transferable structure-gating and convergence-diagnostic protocols, positioning atomistic simulation as a quantitative complement to single-molecule spectroscopy.

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Cite

BibTeXRIS
BibTeX
@article{zhang2026mechanical,
  title = {{Mechanical Rupture of DNA Tension-Gate Elements: Thresholds, Kinetics, and Energetics from Steered Molecular Dynamics}},
  author = {Yonghui Zhang and Yujia Zhou},
  journal = {Biomolecules},
  year = {2026},
  month = nov,
  doi = {10.3390/biom16111586},
  url = {https://www.mdpi.com/2218-273X/16/11/1586},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Mechanical Rupture of DNA Tension-Gate Elements: Thresholds, Kinetics, and Energetics from Steered Molecular Dynamics
AU  - Yonghui Zhang
AU  - Yujia Zhou
PY  - 2026
DA  - 2026/11/01
JO  - Biomolecules
DO  - 10.3390/biom16111586
UR  - https://www.mdpi.com/2218-273X/16/11/1586
AB  - The kinetics and energetics of load-driven conformational rearrangements underlie DNA replication, repair, and DNA nanodevice function. DNA tension-gate tethers exploit these dynamics, yet their rupture thresholds are set almost exclusively by single-molecule calibration; here, an atomistic steered-molecular-dynamics pipeline predicts relative thresholds and characterizes the underlying rearrangements. Seven constructs—duplexes of varying length and GC content, single-stranded poly(dT)30, a GC-clamped hairpin, and G-quadruplex—were pulled with 50 trajectories per construct per rate (0.01/0.001 nm/ps). At MD loading rates, the ordering G-quadruplex (911 pN) > GC-rich duplex (786 pN) > hairpin (643 pN) > mixed duplexes (559/558 pN) > ssDNA (388 pN) holds at both rates, and the design rules deconfound, +68 pN for GC content (47% → 100%), −160 pN for doubled length, and 208 pN for pull geometry—larger than GC itself. Dissipated work falls 31–58% at the slower rate; slow-rate Jarzynski estimators converge for low-dissipation elements, while fast-rate profiles of high-dissipation motifs do not. Absolute thresholds at experimental rates remain out of reach, but the ordering—the actionable output for TGT design—comes with transferable structure-gating and convergence-diagnostic protocols, positioning atomistic simulation as a quantitative complement to single-molecule spectroscopy.
SN  - 2218-273X
ER  -