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

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.