Single-Molecule Dynamics of Nucleic Acids

Single-molecule studies of nucleic acids have transformed our understanding of DNA and RNA by allowing direct measurement of real-time conformational changes, mechanical responses and interaction dynamics of individual molecules. Techniques such as optical and magnetic tweezers, single-molecule fluorescence and atomic force microscopy provide precise control over forces, torques and spatial positioning at the piconewton and nanometre scales. These methods have revealed the energy landscapes governing supercoiling, bending, twisting, strand separation and base-pair melting, and have elucidated how nucleic acids respond to protein binding, chemical modification and environmental cues. By integrating single-molecule experiments with molecular dynamics simulations, researchers now obtain quantitative, atomistic insight into the mechanisms that underpin replication, transcription and genome organisation, offering new perspectives on cellular processes and routes to therapeutic innovation.

Research from Nature Portfolio

Recent studies have applied integrated force-spectroscopy platforms to probe the dynamic structures of single DNA under controlled torsional and tensile constraints. The COMBI-Tweez approach combines optical trapping, time-resolved magnetic tweezers and fluorescence imaging to induce and visualise higher-order DNA motifs such as plectonemes, quantitatively mapping how twist and stretch drive structural transitions. In parallel, cryo-electron tomography of DNA minicircles, supported by molecular dynamics simulations, has unveiled the conformational diversity of both negative and positive supercoiled topoisomers, demonstrating unexpected heterogeneity in three-dimensional shapes under torsional stress. These advances enable precise characterisation of torsional energy landscapes and atomistic views of DNA mechanics in physiological conditions.

Single-Molecule Dynamics of Nucleic Acids publication trend

The graph below shows the total number of articles in single-molecule dynamics of nucleic acids across all publications each year (not limited to Nature Index journals).

Technical terms

Optical tweezers: A laser-based method that traps and applies controlled piconewton forces to single molecules.

Magnetic tweezers: A technique that exerts torque and force on magnetic beads attached to nucleic acids to measure stretching and twisting dynamics.

Fluorescence microscopy: An imaging approach that uses fluorescent labels to monitor the location and conformational changes of individual molecules.

Plectoneme: A supercoiled DNA structure formed by the interwound twisting of the double helix under torsional stress.

Molecular dynamics simulation: A computational method modelling the time-dependent evolution of atomic coordinates to predict molecular behaviour.

Debye screening length: The characteristic distance over which electrostatic interactions are reduced by mobile ions in solution.

References

1. Correlating fluorescence microscopy, optical and magnetic tweezers to study single chiral biopolymers such as DNA. Nature Communications (2024).
2. Structural diversity of supercoiled DNA. Nature Communications (2015).
3. The origin of different bending stiffness between double-stranded RNA and DNA revealed by magnetic tweezers and simulations. Nucleic Acids Research (2024).
4. Electric Field of DNA in Solution: Who Is in Charge?. Physical Review X (2024).
5. Dinuclear complex-induced DNA melting. Journal of Nanobiotechnology (2023).