Platinum-based chemotherapeutic drugs, such as cisplatin, work by covalently binding to DNA, inducing severe local structural changes. Numerous proteins, including DNA repair and tumor-suppressor proteins, recognize these structural changes induced by the drug-DNA adducts. Some of these protein-DNA interactions lead to arrest of the cell cycle and apoptosis of the cancer cells, which leads to high cure rates for certain cancers. However, some protein-DNA interactions lead to repair of the drug-DNA adduct and resistance to the drug. In order to circumvent and develop better drug, one needs to understand the molecular-mechanism underlying differential recognition of the various drug-DNA adducts. We use atomistic molecular dynamics simulations to probe the thermodynamic and structural differences in protein-drug-DNA complexes with the goal of engineering new drugs with desirable protein interactions.

Molecular dynamics simulation studies of recognition of anticancer drug-induced DNA damage by repair proteins

242nd National Meeting (2011)

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