Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

A comprehensive computational mutation structure-function approach for determining potential drug target sites in poliovirus 2A protease

Amna Younus , Muhammad Faraz Bhatti

Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Sector H-12, Kashmir Highway, Islamabad 44000, Pakistan;

For correspondence:- Amna Younus Email: amnayounus82@yahoo.com Tel:+923055869935

Accepted: 16 November 2017 Published: 29 December 2017

Citation: Younus A, Bhatti MF. A comprehensive computational mutation structure-function approach for determining potential drug target sites in poliovirus 2A protease. Trop J Pharm Res 2017; 16(12):2831-2841 doi: 10.4314/tjpr.v16i12.6

© 2017 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To investigate a computational approach for analysing the structure-function relationship of poliovirus 2A protease using various bioinformatics tools.

Methods: The three-dimensional structure of 2Apro was modelled and analyzed using the crystal structure of coxsakievirus B4 as a template to understand the function of this protein. Structural validation programs, VADAR and QMEAN, were used to verify the 2Apro model. Analysis of protein stability changes in poliovirus 2A protease-mutated sequences using various servers was also performed. Furthermore, mutation pattern, intrinsic disorder regions (IDRs), hydrophobic regions, drug binding sites (DBS) and subcellular localization were identified.

Results: Hydrophobicity results confirmed the suitability and reliability of 2A protease as a potential drug target. Less IDRs were observed in the protein. Moreover, the results showed the presence of various important drug binding targets among conserved regions of the protease. The predicted drug binding sites indicate their suitability for the inhibition and development of anti-viral drugs against poliovirus 2A protease.

Conclusion: The current study resulted in the detection of important ligand interactions with respect to the binding site of the targeted protein. Thus, these compounds may be potent drug candidates and their potency may be increased against poliovirus 2A protease with relatively simple structural changes

Keywords: 2A Protease, Computational analysis, Drug binding sites, Intrinsic disorder regions, Hydrophobicity