Departamento de Farmacia, Facultad de Quimica, P. Universidad Catolica de Chile, Macul-Santiago, Chile.
J Mol Model. 2012 May;18(5):2055-64. doi: 10.1007/s00894-011-1224-z. Epub 2011 Sep 6.
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.
克氏锥虫谷氨酰胺半胱氨酸连接酶（TcGCL）被认为是开发新型抗查加斯病药物的潜在药物靶点。我们使用了多种计算方法来研究 TcGCL 与谷胱甘肽（GSH）之间的相互作用。使用酿酒酵母谷氨酸半胱氨酸连接酶作为模板，通过比较建模方法构建了 TcGCL 的三维结构。分子动力学模拟用于验证 TcGCL 模型并分析与 GSH 的分子相互作用。通过均方根偏差聚类，确定了最常见的 GSH 结合模式，并注意了参与分子相互作用的残基。使用 GSH 结合模式来提出药效团模型，可进一步用于识别新型抗查加斯病化合物。
