Searching for sequence features that control DNA cyclizability
Margarita Gordiychuk1, Jonghan Park2, Aakash Basu3,4
1Department of Physics and Astronomy, Johns Hopkins University, Baltimore, MD 21218, USA.
PNAS Nexus
|June 8, 2026
Summary
DNA mechanics are sequence-dependent at short lengths. We developed a statistical model to predict DNA cyclizability based on nucleotide sequences, advancing understanding for DNA nanotechnology.
Area of Science:
- Molecular Biology
- Biophysics
- Polymer Physics
Background:
- DNA mechanical properties are vital for biological functions like DNA packaging and transcription.
- While long DNA follows polymer models, short DNA mechanics, relevant to DNA-protein interactions, are sequence-dependent.
- DNA cyclizability, the tendency to bend and form loops, is a key mechanical property influenced by DNA sequence.
Purpose of the Study:
- To develop a statistical-mechanics framework to systematically analyze sequence-dependent DNA cyclizability.
- To identify the minimal sequence features governing DNA cyclizability.
- To predict DNA sequences with high and low cyclizability.
Main Methods:
- Developed a statistical-mechanics framework to analyze DNA cyclizability based on nucleotide sequences.
- Applied the framework to analyze large datasets of random and biological DNA sequences.
- Validated predictions using all-atom molecular dynamics simulations.
Main Results:
- Identified a minimal pairwise model accurately describing sequence-dependent DNA cyclizability.
- Extracted key sequence features that dictate DNA cyclizability.
- Successfully predicted and validated sequences with extreme cyclizability properties.
Conclusions:
- The study provides a robust framework for understanding sequence-dependent DNA mechanics.
- Identified sequence features controlling DNA cyclizability have implications for DNA nanotechnology and biological processes.
- Advances the understanding of DNA mechanics at the nanoscale, crucial for DNA packaging and protein interactions.
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