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Analysis of Bacillus anthracis nucleoside hydrolase via in silico docking with inhibitors and molecular dynamics simulation

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Abstract

As the enzyme nucleoside hydrolase (NH) is widely found in nature but has not yet been detected in mammals, it is considered an ideal target in the development of chemotherapy against parasitic diseases and bacterial infections like anthrax. Considering the risk that this biological warfare agent represents nowadays, the search for new drugs and new molecular targets in the development of chemotherapy against anthrax is imperative. On this basis, we performed docking studies of six known NH inhibitors at the active site of NH from Bacillus anthracis (BaNH). Subsequently, molecular dynamics (MD) simulations of these compounds inside BaNH were carried out in order to complement the docking studies and select the most promising compounds as leads for the design of potential BaNH inhibitors. Most of the docking and MD results obtained agreed well with each other and showed good correlation with experimental data.

Interactions of compound 6 in the active sites of TvNH and BaNH

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Acknowledgments

The authors wish to thank the Brazilian financial agencies Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo ao Ensino e Pesquisa do Estado do Rio de Janeiro (FAPERJ), Fundação de Amparo à Pesquisa do Estado de Minas Gerais (PAPEMIG) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/Ministério da Defesa (CAPES/MD) (Edital PRODEFESA 2008) for financial support, and the Military Institute of Engineering for providing the physical infrastructure and working space.

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Authors and Affiliations

  1. Laboratory of Molecular Modeling Applied to Chemical and Biological Defense (LMCBD), Military Institute of Engineering, Rio de Janeiro, RJ, Brazil

    Ana P. Guimarães, Aline A. Oliveira & Tanos C. C. França

  2. Chemistry Department, Federal University of Lavras, Lavras, MG, Brazil

    Ana P. Guimarães, Elaine F. F. da Cunha & Teodorico C. Ramalho

Authors
  1. Ana P. Guimarães
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  2. Aline A. Oliveira
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  3. Elaine F. F. da Cunha
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  4. Teodorico C. Ramalho
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  5. Tanos C. C. França
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Correspondence to Teodorico C. Ramalho or Tanos C. C. França.

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Guimarães, A.P., Oliveira, A.A., da Cunha, E.F.F. et al. Analysis of Bacillus anthracis nucleoside hydrolase via in silico docking with inhibitors and molecular dynamics simulation. J Mol Model 17, 2939–2951 (2011). https://doi.org/10.1007/s00894-011-0968-9

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  • DOI: https://doi.org/10.1007/s00894-011-0968-9

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