AI and advanced microscopy reveal intertwined DNA structures with nanometer accuracy

Although often presented in schools as neat double helixes, scientists reveal the diverse and complex shapes of DNA molecules.

DNA is a molecule found in almost all living cells. Because the molecules are long, you end up twisting and entwining yourself in the end. Enzymes in the body try to regulate this process, but if they fail, they can destroy normal activity within the cells, causing disease health and can lead to diseases such as cancer and neurodegeneration.

To find a cure for a major illness, scientists need to understand the complex shape of DNA tangles. Existing lab methods allow you to plot the shape and structure of DNA tangles, but this is both tedious and time-consuming.

An international science team led by the University of Sheffield in the UK is currently automating the process. Using nuclear power microscopy, advanced computer software, and what is known as AI, DNA molecules can be visualized, routes tracked, and measured.

To understand how DNA changes, a field of science known as DNA topology, researchers need to conduct analysis at the nanoscale. The nanometers are 1 billion meters.

Alice Pine, a professor of biophysics at the University of Sheffield, oversaw the research. “This is the first time we have been able to determine the structure of individual complex DNA structures found in cells with nanometer accuracy.

“This allows us to see and understand the meaning of complex structures that can form within cells during normal and abnormal cellular processes such as DNA replication. From here we can explore how these complex topologies and structures affect proteins that interact with the genome, and how they affect anticancer targets such as topoisomases, such as major antibiotics and which antibiotics (enzymes) that are anticancer targets.

“DNA is a really long molecule. Cellular DNA is entangled and tied together. How DNA is tangled,” says Dr. Sean Collome, co-author of the Molecular Bioscience School and Research at the University of Glasgow.

“At each DNA crossing, you can see which DNA is what it is. This allows you to communicate the difference between a single knot and its mirror image. This is important in your research.”

Atomic power microscopes use small probes to physically measure objects under analysis rather than light or electrons like other types of microscopes. This difference makes it suitable for nanoscale analysis.

“Molecular simulations help us understand how DNA interacts with MICA surfaces in AFM experiments,” says Dušan Račko of the Polymer Research Institute at the Slovak Academy of Science, who was involved in the study. “By developing advanced models, we can generate thousands of molecular structures and train future AI frameworks.

This study is the culmination of international research cooperation involving scientists from six universities and research institutes across the UK, Slovakia and France.