Significance of ligand tails for interaction with the minor groove of B-DNA

Minor groove binding ligands are of great interest due to their extraordina ry importance as transcription controlling drugs. We performed three molecu lar dynamics simulations of the unbound d(CGCGAATTCGCG)(2) dodecamer and it s complexes with Hoechst33258 and Netropsin. The structural behavior of the piperazine tail of Hoechst33258, which has already been shown to be a cont ributor in sequence-specific recognition, was analyzed. The simulations als o reveal that the tails of the ligands are able to influence the width of t he minor groove. The groove width is even sensitive for conformational tran sitions of these tails, indicating a high adaptability of the minor groove. Furthermore, the ligands also exert an influence on the B-I/B-II backbone conformational substate behavior. All together these results are important for the understanding of the binding process of sequence-specific ligands.