Molecular dynamics simulations exploring the interaction between DNA and metalated bleomycin

Bleomycin (Blm) is a natural antibiotic with antitumour activity, used as a combination drug in treatment of various types of cancers. Blm intercalates with DNA and will in the presence of a redox metal ion and molecular oxygen form an activated bleomycin complex capable of releasing free radicals and subsequently leading to DNA cleavage. The present theoretical work was carried out to better understand the interaction between DNA and Blm using different metal co-factors (Co and Fe). Binding energies and structural properties were analysed for both the complexes. The results show that Blm binds stronger to DNA when complexed with Fe, and provides a better structural orientation compared to the CoBlm complex in order to abstract the H4' hydrogen of deoxyribose that initiates the DNA strand cleavage process. The short distance between the iron-bound peroxide and the deoxyribose H4' furthermore supports the previously proposed direct abstraction mechanism.