Apr 18, 2016

Mechanisms of small molecule-DNA interactions probed by single-molecule force spectroscopy

Nucleic Acids Research
Ali A AlmaqwashiMark C Williams

Abstract

There is a wide range of applications for non-covalent DNA binding ligands, and optimization of such interactions requires detailed understanding of the binding mechanisms. One important class of these ligands is that of intercalators, which bind DNA by inserting aromatic moieties between adjacent DNA base pairs. Characterizing the dynamic and equilibrium aspects of DNA-intercalator complex assembly may allow optimization of DNA binding for specific functions. Single-molecule force spectroscopy studies have recently revealed new details about the molecular mechanisms governing DNA intercalation. These studies can provide the binding kinetics and affinity as well as determining the magnitude of the double helix structural deformations during the dynamic assembly of DNA-ligand complexes. These results may in turn guide the rational design of intercalators synthesized for DNA-targeted drugs, optical probes, or integrated biological self-assembly processes. Herein, we survey the progress in experimental methods as well as the corresponding analysis framework for understanding single molecule DNA binding mechanisms. We discuss briefly minor and major groove binding ligands, and then focus on intercalators, which have been probed ext...Continue Reading

  • References95
  • Citations11

References

  • References95
  • Citations11

Citations

Mentioned in this Paper

Study
Covalent Interaction
Molecular Helix
Complex (molecular entity)
Helix (Snails)
BAG3
Microscopy, Atomic Force
Binding Protein
Major Groove
Pharmacologic Substance

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