Mechanical Fingerprints of DNA Drug Complexes

Abstract

We have investigated in detail the effects of different minor groove binders and intercalators on the mechanical properties of single DNA molecules under mechanical tension. It is known that individual double stranded DNA molecules show a highly cooperative overstretching transition and may be separated into single strands by application of force. Here we detect non-covalent binding to DNA by mechanical means in AFM based single molecule stretching experiments. The binding of small molecules is found to change the mechanical properties of DNA under tension significantly, and the effects of different binding modes and concentrations are compared. The observed forces and widths of the overstretching transition are found to correlate with magnitudes and ranges of temperatures recorded in DNA thermal melting experiments in the presence of each drug.