Abstract: Molecular dynamics simulations were used to investigate the interaction of DB921 with the DNA oligonucleotide d[CGCGAATTCGCG]2. A 7 ns MD calculation was performed to study the DB921-DNA complex and the results indicated that DB921 was inserted in the minor groove of DNA, binding to the region of duplex AATTC bases. A water molecule forms bifurcated pair of H-bonds between the N atom of benzimidazole ring and N3 atom of the adenine 5 in the DB921-DNA complex. This water molecule performs a key bridging role which induces a more favorable curvature configuration and matches well the DNA minor groove topology. Molecular dynamics studies complemented the structural analysis and offered a clear picture of the water-bridge, providing the theoretical guidance for the design of biologically active minor groove agents.

Key words: Minor grove binding, Diamidine, Water molecule, Molecular recognition