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Probing Structural Variants of Irregular DNA G-Tracts (N ≤ 2) Using MspA Nanopores
Jiadun Liu1, Luoan Xiong2, Yuhang Hu1
1School of Microelectronics, MOE Engineering Research Center of Integrated Circuits for Next Generation Communications, Southern University of Science and Technology, Shenzhen 518055, China.
ACS Applied Materials & Interfaces
|February 20, 2025
Summary
This study explores bilayered G-quadruplexes using nanopore experiments and simulations. Results reveal distinct event types and dynamics for AS1411, AT11, and Z-G4, aiding aptamer identification for diagnostics and therapies.
Area of Science:
- Biophysics
- Nanotechnology
- Genomics
Background:
- Guanine-rich DNA with short G-tracts (≤2 Gs) are common in the human genome and linked to diseases.
- Bilayered G-quadruplexes with G2 tracts are underexplored compared to conventional structures.
Purpose of the Study:
- Investigate unwinding strengths and dynamics of bilayered G-quadruplexes.
- Characterize interactions of AS1411, AT11, and Z-G4 with nanopores.
Main Methods:
- Nanopore experiments in an electric field.
- All-atom molecular dynamics simulations.
- Analysis of current blockage fractions and dwell times.
Main Results:
- AS1411, AT11, and Z-G4 showed distinct interactions with the M2-MspA nanopore, forming two main event types (I and II).
- Z-G4 exhibited a new event type (III), indicating increased rigidity.
- Z-G4 displayed voltage-dependent dynamics with longer dwell times for docking and partial unwinding compared to AT11.
Conclusions:
- Nanopore experiments revealed fewer structural populations than expected for AS1411, explained by reversible docking and translocation.
- Findings advance understanding of complex G-quadruplex folding principles.
- This work facilitates rapid identification of nucleic acid aptamers for molecular diagnostics and targeted therapies.
