Identification of binding mechanisms in single molecule-DNA complexes

Rainer Eckel, Robert Ros, Alexandra Ros, Sven David Wilking, Norbert Sewald, Dario Anselmetti

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

Abstract

Changes in the elastic properties of single deoxyribonucleic acid (DNA) molecules in the presence of different DNA-binding agents are identified using atomic force microscope single molecule force spectroscopy. We investigated the binding of poly(dG-dC) dsDNA with the minor groove binder distamycin A, two supposed major groove binders, an α-helical and a 310-helical peptide, the intercalants daunomycin, ethidium bromide and YO, and the bis-intercalant YOYO. Characteristic mechanical fingerprints in the overstretching behavior of the studied single DNA-ligand complexes were observed allowing the distinction between different binding modes. Docking of ligands to the minor or major groove of DNA has the effect that the intramolecular B-S transition remains visible as a distinct plateau in the force-extension trace. By contrast, intercalation of small molecules into the double helix is characterized by the vanishing of the B-S plateau. These findings lead to the conclusion that atomic force microscope force spectroscopy can be regarded as a single molecule biosensor and is a potent tool for the characterization of binding motives of small ligands to DNA.

Original languageEnglish (US)
Pages (from-to)1968-1973
Number of pages6
JournalBiophysical journal
Volume85
Issue number3
DOIs
StatePublished - Sep 1 2003
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics

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