Metabolic pathway analysis and molecular docking analysis for identification of putative drug targets in Toxoplasma gondii: novel approach



Budhayash Gautam1*, Gurmit Singh2, Gulshan Wadhwa3, Rohit Farmer1, Satendra Singh1, Atul Kumar Singh3, Prashant Ankur Jain1, Pramod Kumar Yadav1



1Department of Computational Biology & Bioinformatics, Jacob School of Biotechnology and Bioengineering, Sam Higginbottom Institute of Agriculture, Technology and Sciences-Deemed to be University, Allahabad-211007, India; 2Department of Computer Science and Information Technology, Shepherd School of Engineering and Technology, Sam Higginbottom Institute of Agriculture, Technology and Sciences-Deemed to be University, Allahabad-211007, India; 3Apex Bioinformatics Centre, Department of Biotechnology, Ministry of Science and Technology, CGO complex, Lodhi Road, New Delhi – 110 003, India.


Email; *Corresponding author


Article Type




Received January 09, 2012; Accepted January 17, 2012; Published February 03, 2012



Toxoplasma gondii is an obligate intracellular apicomplexan parasite that can infect a wide range of warm-blooded animals including humans. In humans and other intermediate hosts, toxoplasma develops into chronic infection that cannot be eliminated by host’s immune response or by currently used drugs. In most cases, chronic infections are largely asymptomatic unless the host becomes immune compromised. Thus, toxoplasma is a global health problem and the situation has become more precarious due to the advent of HIV infections and poor toleration of drugs used to treat toxoplasma infection, having severe side effects and also resistance have been developed to the current generation of drugs. The emergence of these drug resistant varieties of T. gondii has led to a search for novel drug targets. We have performed a comparative analysis of metabolic pathways of the host Homo sapiens and the pathogen T. gondii. The enzymes in the unique pathways of T. gondii, which do not show similarity to any protein from the host, represent attractive potential drug targets. We have listed out 11 such potential drug targets which are playing some important work in more than one pathway. Out of these, one important target is Glutamate dehydrogenase enzyme; it plays crucial part in oxidation reduction, metabolic process and amino acid metabolic process. As this is also present in the targets of tropical diseases of TDR (Tropical disease related Drug) target database and no PDB and MODBASE 3D structural model is available, homology models for Glutamate dehydrogenase enzyme were generated using MODELLER9v6. The model was further explored for the molecular dynamics simulation study with GROMACS, virtual screening and docking studies with suitable inhibitors against the NCI diversity subset molecules from ZINC database, by using AutoDock-Vina. The best ten docking solutions were selected (ZINC01690699, ZINC17465979, ZINC17465983, ZINC18141294_03, ZINC05462670, ZINC01572309, ZINC18055497_01, ZINC18141294, ZINC05462674 and ZINC13152284_01). Further the Complexes were analyzed through LIGPLOT. On the basis of Complex scoring and binding ability it is deciphered that these NCI diversity set II compounds, specifically ZINC01690699 (as it has minimum energy score and one of the highest number of interactions with the active site residue), could be promising inhibitors for T. gondii using Glutamate dehydrogenase as Drug target.



Homology modeling, Molecular dynamics, Docking, Metabolic Pathway Analysis, Glutamate dehydrogenase, Toxoplasma gondii, Structural biology, Drug targets, KEGG.



Gautam et al. Bioinformation 8(3): 134-141 (2012)

Edited by

P Kangueane






Biomedical Informatics



This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.