Paper Title :Protein Structure Modelling, Ligand Docking and Active Site Analysis of Mutated Poliovirus 2a Protease Gene Isolated From the Blood of Pakistani Polio Infected Patients
Author :Amna Younus, Muhammad Faraz Bhatti, Tahir Ahmad, Nasar Virk, Muhammad Arshad, Hussnain Ahmed Janjua
Article Citation :Amna Younus ,Muhammad Faraz Bhatti ,Tahir Ahmad ,Nasar Virk ,Muhammad Arshad ,Hussnain Ahmed Janjua ,
(2016 ) " Protein Structure Modelling, Ligand Docking and Active Site Analysis of Mutated Poliovirus 2a Protease Gene Isolated From the Blood of Pakistani Polio Infected Patients " ,
International Journal of Advances in Science, Engineering and Technology(IJASEAT) ,
pp. 52-57,
Volume-4,Issue-3, Spl. Iss-2
Abstract : Pakistan is among those countries that has reported alarmingly high number of polio cases during the last few
years. Recently, the occurrence of wild poliovirus type 1 and circulating vaccine-derived poliovirus in some cases have been
reported in Pakistan. 2A is multifunctional cysteine protease that performs key role in poliovirus replication that involves
viral polyprotein self-processing and shutting down host cell protein synthesis cleavage of the eukaryotic initiation factor 4G
(eIF4G) proteins. In this study, polio infected blood samples was extracted following 2A protease amplification, cloning and
sequencing and analyzed for mutations. 3D structures of mutated poliovirus 2A protease (PV 2Apro) were determined
through homology modelling using template-based structure prediction method. Predicted models were validated using
different bioinformatics tools. Docking study was performed on selected models via MOE-Dock program to evaluate binding
interactions of four ligands with 2Apro. The best conformations of ligands were analyzed for binding interactions with the
residues of binding cavity of target protease. Certain point mutations were found in the 2Apro sequences. These mutations
after in silico analysis proved to be involved in the active site binding with certain inhibitors. Our findings highlight the role
of the mutations in the binding cavity along with the identification of potential binding sites of the protease. We conclude
that after entering into the body, polio virus undergoes some changes in the form of mutations of 2Apro contributing to the
replication of virus which would help in formulating new drugs to inhibit polio virus replication.
Keywords- 2Aprotease, Docking, Inhibitors, Mutations, Pakistan, Poliovirus
Type : Research paper
Published : Volume-4,Issue-3, Spl. Iss-2
DOIONLINE NO - IJASEAT-IRAJ-DOIONLINE-5676
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Published on 2016-10-22 |
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