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Molecular dynamics simulation of non-covalent interactions between polynuclear platinum(II) complexes and DNA

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Abstract

Several studies with substitution-inert polynuclear platinum(II) complexes (SI-PPC) have been carried out in recent years due to the form of DNA binding presented by these compounds. This form of bonding is achieved by molecular recognition through the formation of non-covalent structures, commonly called phosphate clamps and forks, which generate small extensions of the major and minor grooves. In this work, we use molecular dynamics simulations (MD) to study the formation of these cyclical structures between six different SI-PPCs and a double DNA dodecamer, here called 24_bp_DNA. The results showed the influence of the complex expressed on the number of phosphate clamps and forks formed. Based on the conformational characterization of the DNA fragment, we show that the studied SI-PPCs interact preferentially in the minor groove, causing groove spanning, except for two of them, Monoplatin and AH44. The phosphates of C–G pairs are the main sites for such non-covalent interactions. The Gibbs interaction energy of solvated species points out to AH78P, AH78H, and TriplatinNC as the most probable ones when coupled with DNA. As far as we know, this work is the very first one related to SI-PPCs which brings MD simulations and a complete analysis of the non-covalent interactions with a double DNA dodecamer.

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Acknowledgements

We would like to thank the Brazilian funding agencies CAPES, CNPq for the financial support, and FAPEMIG (Project APQ-00591-15) that allowed the purchase of the Nvidia graphics processing unit (GPU) used to speed up our MD simulations. LASC would like to acknowledge CNPq for the research Grant (307887/2018-9); LASC is also member of the Rede Mineira de Química (RQ-MG). NMPR would like to thank CAPES for her Ph.D. scholarship. The authors would like to thank Prof. H. F. Dos Santos (NEQC-UFJF) for carefully reading the manuscript.

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  1. NEQC-Núcleo de Estudos em Química Computacional, Departamento de Química, ICE, Universidade Federal de Juiz de Fora, Juiz de Fora, MG, 36036-900, Brazil

    Nathália M. P. Rosa, Júlio A. F. Arvellos & Luiz Antônio S. Costa

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  1. Nathália M. P. Rosa
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NMPR is Ph.D. at NEQC-UFJF. This work is part of her thesis and she was responsible for all DFT calculations, MD simulations, and writing this manuscript; JAFA was member of NEQC where he got the Master’s degree. He was also responsible for MD simulations. LASC is co-head of the NEQC and Nathália’s and Júlio’s supervisor. He was also responsible for the analysis and careful reading of the manuscript.

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Correspondence to Luiz Antônio S. Costa.

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Rosa, N.M.P., Arvellos, J.A.F. & Costa, L.A.S. Molecular dynamics simulation of non-covalent interactions between polynuclear platinum(II) complexes and DNA. J Biol Inorg Chem 25, 963–978 (2020). https://doi.org/10.1007/s00775-020-01817-9

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