In Silico and in Vitro Studies: Tryparedoxin Peroxidase Inhibitor Activity of Methotrexate for Antileishmanial Activity
Ravi Kumar Gundampati, Shraddha Sahu, Avinash Kumar Srivastava, Sambamurthy Chandrasekaran, Parameswara Rao Vuddanda, Rajesh Kumar Pandey, Radheshyam Maurya, Sanjay Singh and Medicherla V. Jagannadham
DOI : 10.3844/ajidsp.2013.117.129
American Journal of Infectious Diseases
Volume 9, Issue 4
In order to understand the mechanism of molecular interactions at the active site of Tryparedoxin Peroxidase (Try P), homology modeling and docking studies were performed. We generated a Three-Dimensional (3D) model of target protein based on the Crystal structure of Leishmania Major Try PI (PDB ID: 3TUE) using modeler software. Docking analysis was carried out to study the effects of methotrexate on Tryparedoxin Peroxidase (Try P). Inhibition of the Tryparedoxin peroxidase interaction has become a new therapeutic strategy in treating leishmaniasis. Docking analysis was carried out to study the effects of methotrexate on Tryparedoxin Peroxidase (TryP). Tryparedoxin peroxidase of Trypanosomatidae family functions as antioxidant through their peroxidase and peroxynitrite reductase activities. The theoretical docking study, conducted on a sample previously reported for anti-cancer properties of Methotrexate at the binding site of 3D models of Tryparedoxin Peroxidase of Leishmania braziliensis (L. braziliensis Try P) examine interaction energy. Our studies indicate that Methotrexate displays potent activity against Try P with lowest binding energy and RMSD values to be -14.5879 Kcal/Mol and 2.0 A. The results of the present study clearly demonstrated the Tryparedoxin Peroxidase inhibitory activity by methotrexate in in silico docking analysis and in vitro assay which contributes towards understanding the mechanism of antileishmanial activity.
© 2013 Ravi Kumar Gundampati, Shraddha Sahu, Avinash Kumar Srivastava, Sambamurthy Chandrasekaran, Parameswara Rao Vuddanda, Rajesh Kumar Pandey, Radheshyam Maurya, Sanjay Singh and Medicherla V. Jagannadham. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.