Structure-Function Mutational Analysis and Prediction of the Potential Impact of High Risk Non-Synonymous Single-Nucleotide Polymorphism on Poliovirus 2A Protease Stability Using Comprehensive Informatics Approaches.

ABSTRACT: Polio viral proteinase 2A performs several essential functions in genome replication. Its inhibition prevents viral replication, thus making it an excellent substrate for drug development. In this study, the three-dimensional structure of 2A protease was determined and optimized by homology modelling. To predict the molecular basis of the interaction of small molecular agonists, docking simulations were performed on a structurally diverse dataset of poliovirus 2A protease (PV2A^pr°) inhibitors. Docking results were employed to identify high risk missense mutations that are highly damaging to the structure, as well as the function, of the protease. Intrinsic disorder regions (IDRs), drug binding sites (DBS), and protein stability changes upon mutations were also identified amo

SUBMITTER: Younus A 

PROVIDER: S-EPMC5977168 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature