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Int. J. Mol. Sci. 2014, 15(1), 75-99; doi:10.3390/ijms15010075
Article

Interaction of Classical Platinum Agents with the Monomeric and Dimeric Atox1 Proteins: A Molecular Dynamics Simulation Study

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Received: 1 November 2013; in revised form: 5 December 2013 / Accepted: 12 December 2013 / Published: 20 December 2013
(This article belongs to the collection Proteins and Protein-Ligand Interactions)
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Abstract: We carried out molecular dynamics simulations and free energy calculations for a series of binary and ternary models of the cisplatin, transplatin and oxaliplatin agents binding to a monomeric Atox1 protein and a dimeric Atox1 protein to investigate their interaction mechanisms. All three platinum agents could respectively combine with the monomeric Atox1 protein and the dimeric Atox1 protein to form a stable binary and ternary complex due to the covalent interaction of the platinum center with the Atox1 protein. The results suggested that the extra interaction from the oxaliplatin ligand–Atox1 protein interface increases its affinity only for the OxaliPt + Atox1 model. The binding of the oxaliplatin agent to the Atox1 protein might cause larger deformation of the protein than those of the cisplatin and transplatin agents due to the larger size of the oxaliplatin ligand. However, the extra interactions to facilitate the stabilities of the ternary CisPt + 2Atox1 and OxaliPt + 2Atox1 models come from the α1 helices and α2-β4 loops of the Atox1 protein–Atox1 protein interface due to the cis conformation of the platinum agents. The combinations of two Atox1 proteins in an asymmetric way in the three ternary models were analyzed. These investigations might provide detailed information for understanding the interaction mechanism of the platinum agents binding to the Atox1 protein in the cytoplasm.
Keywords: molecular dynamics simulations; molecular mechanics Poisson–Boltzmann surface area (MM-PBSA); Atox1 protein; cisplatin; transplaitn; oxaliplatin; interaction mechanism molecular dynamics simulations; molecular mechanics Poisson–Boltzmann surface area (MM-PBSA); Atox1 protein; cisplatin; transplaitn; oxaliplatin; interaction mechanism
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Wang, X.; Li, C.; Wang, Y.; Chen, G. Interaction of Classical Platinum Agents with the Monomeric and Dimeric Atox1 Proteins: A Molecular Dynamics Simulation Study. Int. J. Mol. Sci. 2014, 15, 75-99.

AMA Style

Wang X, Li C, Wang Y, Chen G. Interaction of Classical Platinum Agents with the Monomeric and Dimeric Atox1 Proteins: A Molecular Dynamics Simulation Study. International Journal of Molecular Sciences. 2014; 15(1):75-99.

Chicago/Turabian Style

Wang, Xiaolei; Li, Chaoqun; Wang, Yan; Chen, Guangju. 2014. "Interaction of Classical Platinum Agents with the Monomeric and Dimeric Atox1 Proteins: A Molecular Dynamics Simulation Study." Int. J. Mol. Sci. 15, no. 1: 75-99.


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