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

Luís Fernando Saraiva MacEdo Timmers, Rodrigo G. Ducati, Zilpa Adriana Sánchez-Quitian, Luiz Augusto Basso, Diógenes Santiago Santos, Walter Filgueira De Azevedo

Research output: Contribution to journalArticle

6 Citations (Scopus)

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 2012
Externally publishedYes

Fingerprint

Cytidine Deaminase
tuberculosis
Salvaging
Enzyme activity
inhibitors
Free energy
Molecular dynamics
Recycling
Enzymes
Ligands
molecular dynamics
Proteins
Cytidine
Deoxyuridine
Deoxycytidine
Uridine
Computer simulation
enzyme activity
simulation
pyrimidines

Keywords

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

ASJC Scopus subject areas

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

Cite this

Combining molecular dynamics and docking simulations of the cytidine deaminase from Mycobacterium tuberculosis H37Rv. / Timmers, Luís Fernando Saraiva MacEdo; Ducati, Rodrigo G.; Sánchez-Quitian, Zilpa Adriana; Basso, Luiz Augusto; Santos, Diógenes Santiago; De Azevedo, Walter Filgueira.

In: Journal of Molecular Modeling, Vol. 18, No. 2, 02.2012, p. 467-479.

Research output: Contribution to journalArticle

Timmers, Luís Fernando Saraiva MacEdo ; Ducati, Rodrigo G. ; Sánchez-Quitian, Zilpa Adriana ; Basso, Luiz Augusto ; Santos, Diógenes Santiago ; De Azevedo, Walter Filgueira. / Combining molecular dynamics and docking simulations of the cytidine deaminase from Mycobacterium tuberculosis H37Rv. In: Journal of Molecular Modeling. 2012 ; Vol. 18, No. 2. pp. 467-479.
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