TY - JOUR
T1 - Combining molecular dynamics and docking simulations of the cytidine deaminase from Mycobacterium tuberculosis H37Rv
AU - Timmers, Luís Fernando Saraiva Mac Edo
AU - Ducati, Rodrigo Gay
AU - Sánchez-Quitian, Zilpa Adriana
AU - Basso, Luiz Augusto
AU - Santos, Diógenes Santiago
AU - De Azevedo, Walter Filgueira
N1 - Funding Information:
This work was supported by National Institute of Science and Technology on Tuberculosis (Decit/SCTIE/MS-MCT-CNPq-FNDCTCAPES). D.S.S. (304051/1975-06), L.A.B. (520182/99-5), and W.F.A. Jr. (300851/98-7) are research career awardees of the National Council for Scientific and Technological Development of Brazil (CNPq). Z.A.S.Q. acknowledges a scholarship awarded by CNPq. R.G.D. is a postdoctoral fellow of CNPq. L.F.S.M.T. acknowledges a scholarship awarded by CAPES. L.F.S.M.T. is grateful to Dr. Ernesto Raúl Caffarena for helpful discussions regarding free energy of binding.
PY - 2012/2
Y1 - 2012/2
N2 - 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.
AB - 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.
KW - Free energy of binding
KW - IC determination
KW - Molecular docking simulation
KW - Molecular dynamics simulation
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U2 - 10.1007/s00894-011-1045-0
DO - 10.1007/s00894-011-1045-0
M3 - Article
C2 - 21541749
AN - SCOPUS:84861234064
SN - 1610-2940
VL - 18
SP - 467
EP - 479
JO - Journal of Molecular Modeling
JF - Journal of Molecular Modeling
IS - 2
ER -