Combining molecular dynamics and docking simulations of the cytidine deaminase from Mycobacterium tuberculosis H37Rv

Luís Fernando Saraiva Mac Edo Timmers, Rodrigo Gay Ducati, Zilpa Adriana Sánchez-Quitian, Luiz Augusto Basso, Diógenes Santiago Santos, Walter Filgueira De Azevedo

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Cytidine Deaminase (CD) is an evolutionarily conserved enzyme that participates in the pyrimidine salvage pathway recycling cytidine and deoxycytidine into uridine and deoxyuridine, respectively. Here, our goal is to apply computational techniques in the pursuit of potential inhibitors of Mycobacterium tuberculosis CD (MtCDA) enzyme activity. Molecular docking simulation was applied to find the possible hit compounds. Molecular dynamics simulations were also carried out to investigate the physically relevant motions involved in the protein-ligand recognition process, aiming at providing estimates for free energy of binding. The proposed approach was capable of identifying a potential inhibitor, which was experimentally confirmed by IC 50 evaluation. Our findings open up the possibility to extend this protocol to different databases in order to find new potential inhibitors for promising targets based on a rational drug design process.

Original languageEnglish (US)
Pages (from-to)467-479
Number of pages13
JournalJournal of Molecular Modeling
Volume18
Issue number2
DOIs
StatePublished - Feb 1 2012

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Keywords

  • Free energy of binding
  • IC determination
  • Molecular docking simulation
  • Molecular dynamics simulation

ASJC Scopus subject areas

  • Catalysis
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Computational Theory and Mathematics
  • Inorganic Chemistry

Cite this

Timmers, L. F. S. M. E., Ducati, R. G., Sánchez-Quitian, Z. A., Basso, L. A., Santos, D. S., & De Azevedo, W. F. (2012). Combining molecular dynamics and docking simulations of the cytidine deaminase from Mycobacterium tuberculosis H37Rv. Journal of Molecular Modeling, 18(2), 467-479. https://doi.org/10.1007/s00894-011-1045-0