Open Access“Molecular Modeling and Identification of Inhibitors against Human Mitochondrial Thymidine Kinase 2”
Author(s) -
Ratha Mahendran,
Suganya Jeyabasker,
Sharanya Manoharan,
K. Anbarasu,
Astral Francis
Publication year - 2017
Publication title -
asian journal of pharmaceutical and clinical research
Language(s) - English
Resource type - Journals
eISSN - 2455-3891
pISSN - 0974-2441
DOI - 10.22159/ajpcr.2017.v10i5.17185
Subject(s) - docking (animal) , thiourea , chemistry , thymidine , biochemistry , dna , thymidine kinase , nucleoside , stereochemistry , microbiology and biotechnology , biology , virology , medicine , virus , nursing , organic chemistry , herpes simplex virus
Objective:Mitochondrial disorders linked to Thymidine Kinase 2 (TK2) deficiency is associated to long term treatment with antiviral nucleoside analogues such as AZT (AZidoThymidine). The accumulation of AZT-TP (AZidoThymidine-TriPhosphate) is suggested to affect DNA polymerase, resulting in mtDNA (mitochondrial DNA) depletion. Thus a potent and selective inhibitor for TK2 is essential to be predicted.Methods: The human mitochondrial TK2was modeled usingModeller and the structure was evaluated using Ramachandran plot. The ligand molecule of both the derivatives of deoxythymidine and thioureawere optimized usingChemsketch and were further docked using GLIDE Schrödinger package 2009.Results: The docking results of both Deoxythymidine and Thiourea derivatives against the target TK2 were analyzed to find the ligands with good dock score and Glide energy. The ligands were selected and induced fit docking of both the derivatives were carried out and the interactions were observed usingPyMol.Conclusion: The present study indicates that deoxythymidine derivatives interact significantly and hence serve as selective inhibitors against Human Mitochondrial TK2.Keywords: Thymidine kinase 2, Azidothymidine-triPhosphate, Docking, Grid-based ligand docking with energetics, Deoxythymidine, Thiourea