Shape effects on the activity of synthetic major-groove binding ligands

In this work we present the results of a molecular simulation study of two different tetracationic bis iron(II) supramolecular cylinders interacting with DNA. One cylinder has been shown to bind in the major groove of DNA and to induce dramatic coiling of the DNA; the second is a derivative of the first, with additional methyl groups attached so as to give a larger cylinder-radius. The simulations show that both cylinders bind strongly to the major groove of the DNA, and induce complex structural changes in A–T rich regions. Whereas the parent cylinder tends to bind along the major groove, the derivatised cylinder tends to twist so that only one end remains within the major groove. Both G–C rich and A–T rich binding sites for the derivatised cylinder are discussed.