Molecular modeling of Trypanosoma cruzi glutamate cysteine ligase and investigation of its interactions with glutathione

Carlos F. Lagos, Raul Araya-Secchi, Pablo Thomas, Tomás Pérez-Acle, Ricardo A. Tapia, Cristian O. Salas

Resultado de la investigación: Article

1 Cita (Scopus)

Resumen

Trypanosoma cruzi glutamate cysteine ligase (TcGCL) is considered a potential drug target to develop novel antichagasic drugs. We have used a variety of computational methods to investigate the interactions between TcGCL with Glutathione (GSH). The three-dimensional structure of TcGCL was constructed by comparative modeling methods using the Saccharomyces cerevisiae glutamate cysteine ligase as template. Molecular dynamics simulations were used to validate the TcGCL model and to analyze the molecular interactions with GSH. Using RMSD clustering, the most prevalent GSH binding modes were identified paying attention to the residues involved in the molecular interactions. The GSH binding modes were used to propose pharmacophore models that can be exploited in further studies to identify novel antichagasic compounds.

Idioma originalEnglish
Páginas (desde-hasta)2055-2064
Número de páginas10
PublicaciónJournal of Molecular Modeling
Volumen18
N.º5
DOI
EstadoPublished - may 2012

Huella dactilar

Glutamate-Cysteine Ligase
glutamates
glutathione
Molecular modeling
Molecular interactions
cysteine
Glutathione
Computational methods
Yeast
Molecular dynamics
molecular interactions
interactions
drugs
Computer simulation
saccharomyces
Pharmaceutical Preparations
templates
molecular dynamics
simulation

ASJC Scopus subject areas

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

Citar esto

Lagos, Carlos F. ; Araya-Secchi, Raul ; Thomas, Pablo ; Pérez-Acle, Tomás ; Tapia, Ricardo A. ; Salas, Cristian O. / Molecular modeling of Trypanosoma cruzi glutamate cysteine ligase and investigation of its interactions with glutathione. En: Journal of Molecular Modeling. 2012 ; Vol. 18, N.º 5. pp. 2055-2064.
@article{fa9256ca4cf54e5b88e372f665b821a9,
title = "Molecular modeling of Trypanosoma cruzi glutamate cysteine ligase and investigation of its interactions with glutathione",
abstract = "Trypanosoma cruzi glutamate cysteine ligase (TcGCL) is considered a potential drug target to develop novel antichagasic drugs. We have used a variety of computational methods to investigate the interactions between TcGCL with Glutathione (GSH). The three-dimensional structure of TcGCL was constructed by comparative modeling methods using the Saccharomyces cerevisiae glutamate cysteine ligase as template. Molecular dynamics simulations were used to validate the TcGCL model and to analyze the molecular interactions with GSH. Using RMSD clustering, the most prevalent GSH binding modes were identified paying attention to the residues involved in the molecular interactions. The GSH binding modes were used to propose pharmacophore models that can be exploited in further studies to identify novel antichagasic compounds.",
keywords = "Comparative modeling, Glutamate cysteine ligase, Molecular dynamics, Pharmacophore, Trypanosoma cruzi",
author = "Lagos, {Carlos F.} and Raul Araya-Secchi and Pablo Thomas and Tom{\'a}s P{\'e}rez-Acle and Tapia, {Ricardo A.} and Salas, {Cristian O.}",
year = "2012",
month = "5",
doi = "10.1007/s00894-011-1224-z",
language = "English",
volume = "18",
pages = "2055--2064",
journal = "Journal of Molecular Modeling",
issn = "1610-2940",
publisher = "Springer Verlag",
number = "5",

}

Molecular modeling of Trypanosoma cruzi glutamate cysteine ligase and investigation of its interactions with glutathione. / Lagos, Carlos F.; Araya-Secchi, Raul; Thomas, Pablo; Pérez-Acle, Tomás; Tapia, Ricardo A.; Salas, Cristian O.

En: Journal of Molecular Modeling, Vol. 18, N.º 5, 05.2012, p. 2055-2064.

Resultado de la investigación: Article

TY - JOUR

T1 - Molecular modeling of Trypanosoma cruzi glutamate cysteine ligase and investigation of its interactions with glutathione

AU - Lagos, Carlos F.

AU - Araya-Secchi, Raul

AU - Thomas, Pablo

AU - Pérez-Acle, Tomás

AU - Tapia, Ricardo A.

AU - Salas, Cristian O.

PY - 2012/5

Y1 - 2012/5

N2 - Trypanosoma cruzi glutamate cysteine ligase (TcGCL) is considered a potential drug target to develop novel antichagasic drugs. We have used a variety of computational methods to investigate the interactions between TcGCL with Glutathione (GSH). The three-dimensional structure of TcGCL was constructed by comparative modeling methods using the Saccharomyces cerevisiae glutamate cysteine ligase as template. Molecular dynamics simulations were used to validate the TcGCL model and to analyze the molecular interactions with GSH. Using RMSD clustering, the most prevalent GSH binding modes were identified paying attention to the residues involved in the molecular interactions. The GSH binding modes were used to propose pharmacophore models that can be exploited in further studies to identify novel antichagasic compounds.

AB - Trypanosoma cruzi glutamate cysteine ligase (TcGCL) is considered a potential drug target to develop novel antichagasic drugs. We have used a variety of computational methods to investigate the interactions between TcGCL with Glutathione (GSH). The three-dimensional structure of TcGCL was constructed by comparative modeling methods using the Saccharomyces cerevisiae glutamate cysteine ligase as template. Molecular dynamics simulations were used to validate the TcGCL model and to analyze the molecular interactions with GSH. Using RMSD clustering, the most prevalent GSH binding modes were identified paying attention to the residues involved in the molecular interactions. The GSH binding modes were used to propose pharmacophore models that can be exploited in further studies to identify novel antichagasic compounds.

KW - Comparative modeling

KW - Glutamate cysteine ligase

KW - Molecular dynamics

KW - Pharmacophore

KW - Trypanosoma cruzi

UR - http://www.scopus.com/inward/record.url?scp=84861231883&partnerID=8YFLogxK

U2 - 10.1007/s00894-011-1224-z

DO - 10.1007/s00894-011-1224-z

M3 - Article

C2 - 21894564

AN - SCOPUS:84861231883

VL - 18

SP - 2055

EP - 2064

JO - Journal of Molecular Modeling

JF - Journal of Molecular Modeling

SN - 1610-2940

IS - 5

ER -