HOMOLOGY MODELING AND IN SILICO DOCKING ANALYSIS OF HUMAN MITOCHONDRIAL THYMIDINE KINASE 2 USING GRID-BASED LIGAND DOCKING WITH ENERGETICS

Radha Mahendran; Suganya Jeyabasker; Sharanya Manoharan; Anbarasu Krishnan; Astral Francis

doi:10.22159/ajpcr.2017.v10i5.17185

Authors

Radha Mahendran Dr. RadhaMahendran, Associate Prof/HOD, Bioinformatics Department Vels University, Pallavaram, Chennai-117, Tamil Nadu, India.
Suganya Jeyabasker Department of Bioinformatics, School of Life Sciences, Vels University, Chennai, Tamil Nadu, India.
Sharanya Manoharan Department of Bioinformatics, School of Life Sciences, Vels University, Chennai, Tamil Nadu, India.
Anbarasu Krishnan Department of Bioinformatics, School of Life Sciences, Vels University, Chennai, Tamil Nadu, India.
Astral Francis Department of Bioinformatics, School of Life Sciences, Vels University, Chennai, Tamil Nadu, India.

DOI:

https://doi.org/10.22159/ajpcr.2017.v10i5.17185

Keywords:

Thymidine kinase 2, Azidothymidine-triPhosphate, Docking, Grid-based ligand docking with energetics, Deoxythymidine, Thiourea

Abstract

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 SchrÃ¶dinger 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.

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Author Biography

Radha Mahendran, Dr. RadhaMahendran, Associate Prof/HOD, Bioinformatics Department Vels University, Pallavaram, Chennai-117, Tamil Nadu, India.

Bioinformatics Department

Vels University, Pallavaram,

Chennai-117, Tamil Nadu, India.

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