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Protein–ligand interaction of T. cruzi trans-sialidase inhibitors: a docking and QM/MM MD study

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Abstract

The trans-Sialidase from Trypanosoma cruzi (TcTS) might be a key enzyme in search of new and more effective anti-Trypanosoma cruzi agents. In this report, molecular docking and quantum mechanical/molecular mechanical (QM/MM) molecular dynamics (MD) simulations were employed to determine the binding mode of the three TcTS inhibitors, two quinolinones derivatives (DHQ and THQ) and DANA. The results show that the sulfone group from THQ plays an important role in the protein-inhibitor interactions. In addition, a detailed analysis of the interactions of these inhibitors with key residues inside the binding pocket of TcTS has been carried out using AM1/MM. The residues Asp59, Asp247, Arg35, Arg245, and Arg314 are appointed as key residues to affinity energy of the complexes studied. Finally, the B3LYP/MM and AM1/MM methods were used to calculate global interaction energy, in order to understand the potential of these inhibitors. Among the inhibitors studied, THQ is confirmed as the most efficient one for inhibiting TcTS.

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Acknowledgments

We would like to thank the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo e Desenvolvimento da Pesquisa (FADESP) and Pró-Reitoria de Pesquisa e Pós-Graduação of Universidade Federal do Pará (PROPESP-UFPA) for financial support.

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Authors and Affiliations

  1. Laboratório de Planejamento e Desenvolvimento de Fármacos, Instituto de Ciências Exatas e Naturais, Universidade Federal do Pará, CP 11101, Belém, PA, 66075-110, Brazil

    Anderson Henrique Lima, Jerônimo Lameira & Cláudio Nahum Alves

  2. Instituto de Ciências Biológicas, Universidade Federal do Pará, CP 11101, Belém, PA, 66075-110, Brazil

    Jerônimo Lameira

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  1. Anderson Henrique Lima
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  2. Jerônimo Lameira
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  3. Cláudio Nahum Alves
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Correspondence to Jerônimo Lameira.

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Lima, A.H., Lameira, J. & Alves, C.N. Protein–ligand interaction of T. cruzi trans-sialidase inhibitors: a docking and QM/MM MD study. Struct Chem 23, 147–152 (2012). https://doi.org/10.1007/s11224-011-9854-4

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  • DOI: https://doi.org/10.1007/s11224-011-9854-4

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