Related Experiment Video
Updated: May 5, 2026
05:37
Single-Molecule Fluorescence Visualization of DNA Polymerase Dynamics at G-Quadruplexes
Published on: April 4, 2025
1.2K
Sequence-Encoded Frustration Directs the Formation of Abridged G-Quadruplex Architectures
Yuncheng Qian1, Mohamed Y Ali1, Andreas I Karsisiotis1
1Biomedical Sciences Research Institute, Ulster University, Coleraine, UK.
Angewandte Chemie (International Ed. in English)
|May 4, 2026
Summary
Programmable frustration in DNA sequences guides G-quadruplex folding into stable, compact structures. This design principle enables control over nucleic acid topology and dynamics for novel DNA-based systems.
Area of Science:
- Biochemistry
- Structural Biology
- Computational Biology
Background:
- Frustration, or competing interactions, shapes energy landscapes in proteins and soft matter.
- This principle has been underexplored as a programmable design tool in nucleic acid research.
Purpose of the Study:
- To demonstrate sequence-encoded frustration as a method to program DNA G-quadruplex folding.
- To engineer novel DNA architectures with controlled topology and dynamics.
Main Methods:
- Integrated structural, spectroscopic, and thermodynamic analyses.
- Computational approaches including TD-DFT for spectral assignment.
- Atomic resolution analysis of unfolding pathways.
Main Results:
- Demonstrated that sequence-encoded frustration programs DNA G-quadruplex folding.
- Achieved stable "abridged" G-quadruplex architectures with fewer guanine tetrads.
- Identified a thermodynamically stabilized G-triplex intermediate using TD-DFT computed electronic circular dichroism spectra.
Conclusions:
- Programmable frustration is a predictive design principle for nucleic acid topology and dynamics.
- Offers new strategies for engineering functional DNA-based systems.
- Provides insights into genomic G-quadruplex plasticity.
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