Molecular modeling of Trypanosoma cruzi glutamate cysteine ligase and investigation of its interactions with glutathione
| Autor: | Raul Araya-Secchi, Cristian O. Salas, Tomas Perez-Acle, Carlos F. Lagos, Pablo Thomas, Ricardo A. Tapia |
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| Rok vydání: | 2011 |
| Předmět: |
Glutamate–cysteine ligase
Saccharomyces cerevisiae Proteins Molecular model Glutamate-Cysteine Ligase Trypanosoma cruzi Saccharomyces cerevisiae Molecular Sequence Data Protozoan Proteins Biology Molecular Dynamics Simulation Catalysis Inorganic Chemistry chemistry.chemical_compound Molecular dynamics Amino Acid Sequence Physical and Theoretical Chemistry Binding Sites Organic Chemistry Glutathione biology.organism_classification Molecular medicine Trypanocidal Agents Computer Science Applications Kinetics Computational Theory and Mathematics chemistry Biochemistry Structural Homology Protein Drug Design Thermodynamics Pharmacophore Protein Binding |
| Zdroj: | Journal of molecular modeling. 18(5) |
| ISSN: | 0948-5023 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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