Theoretical studies on binding modes of copper-based nucleases with DNA

• Molecular docking predicts groove binding and electrostatic interaction well for the studied copper nucleases.
• The DNA binding affinity of copper nucleases influenced by the ligand size, length, functional groups, chelate ring size bound to copper center.
• Intercalation modes could be reproduced by “distorted DNA” formed by molecular dynamics simulations.
• MM-PBSA approach validated the DNA binding affinity of copper nuclease.

In the present work, molecular simulations were performed for the purpose of predicting the binding modes of four types of copper nucleases (a total 33 compounds) with DNA. Our docking results accurately predicted the groove binding and electrostatic interaction for some copper nucleases with B-DNA. The intercalation modes were also reproduced by “gap DNA”. The obtained results demonstrated that the ligand size, length, functional groups and chelate ring size bound to the copper center could influence the binding affinities of copper nucleases. The binding affinities obtained from the docking calculations herein also replicated results found using MM-PBSA approach. The predicted DNA binding modes of copper nucleases with DNA will ultimately help us to better understand the interaction of copper compounds with DNA.

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