DNA is the molecule that nature uses as genetic material and it rarely exists in a relaxed state. Rather, it is subjected to torsional, bending or stretching stress generated in cellular processes such as recombination, gene expression, replication, and more generally protein recognition. These tensions cause severe distortions on the double helix, which, in turn, influence its dynamic and recognition properties. Our group is focused on modelling DNA fragments longer than 300 bp at atomic resolution under mechanical stress, which causes the formation of complex spatial arrangements. This nano length-scale is the missing link between crystallographic structures, which usually contain short DNA fragments (up to 20 bp), and force-extension experiments, which are applied to DNA molecules of some kbps. The use of the supercomputer Bede has enabled us to study stretched, bent, and supercoiled DNA, together with its melting caused by the action of cellular motors. All these aspects of the molecule of DNA are relevant for understanding its functionality inside living beings.
Executive summary of project results
When aiming for atomic detail, DNA has typically been characterized using short, relaxed fragments (up to 50 base pairs or bp). However, inside cells, DNA is a very long polymer that is supercoiled, subjected to bending and pulling forces, and surrounded by a crowded environment. In our lab, we have developed approaches and protocols for simulating DNA at the atomic level while accounting for these mechanical stresses in order to recreate more realistic conditions. We have produced an understanding of how DNA structure and dynamics respond to supercoiling when combined with pulling and DNA-bending proteins. In addition, I have provided atomistic highlights of how sequences such as A-tracts introduce global DNA curvature on a larger scale.
How has using Bede helped in your research?
Bede is essential for producing the main data for our lab, it has meant we have been able to produce high-quality publications that have supported several grant applications.
Publications
Atomic description of the reciprocal action between supercoils and melting bubbles on linear DNA. M Burman and A Noy (2025) Phys Rev Lett, 134, 038403 https://doi.org/10.1103/PhysRevLett.134.038403.
The impact of sequence periodicity on DNA elasticity: investigating the origin of A-tract’s curvature. Gardasevic and A. Noy (2024). Nanoscale, 16, 18410 – 18420. https://doi.org/10.1039/D4NR02571G
Correlating fluorescence microscopy, optical, and magnetic tweezers to study single chiram biopolymers such as DNA. JW Shepherd, S Guilbaud, Z Zhou, J Howard, M Burman, C Schaefer, A Kerrigan, C Steele-King, A Noy, and MC Leake (2024). Nature Communications, 15, 2748 https://www.nature.com/articles/s41467-024-47126-6
