Structural insights on identification of potential lead compounds targeting WbpP in Vibrio vulnificus through structure-based approaches

Journal of Receptor and Signal Transduction Research
Dakshinamurthy SasikalaPappu Srinivasan

Abstract

WbpP encoding UDP-GlcNAC C4 epimerase is responsible for the activation of virulence factor in marine pathogen Vibrio vulnificus (V. vulnificus) and it is linked to many aquatic diseases, thus making it a potential therapeutic target. There are few reported compounds that include several natural products and synthetic compounds targeting Vibrio sp, but specific inhibitor targeting WbpP are unavailable. Here, we performed structure-based virtual screening using chemical libraries such as Binding, TOSLab and Maybridge to identify small molecule inhibitors of WbpP with better drug-like properties. Deficient structural information forced to model the structure and the stable protein structure was obtained through 30 ns of MD simulations. Druggability regions are focused for new lead compounds and our screening protocol provides fast docking of entire small molecule library with screening criteria of ADME/Lipinski filter/Docking followed by re-docking of top hits using a method that incorporates both ligand and protein flexibility. Docking conformations of lead molecules interface displays strong H-bond interactions with the key residues Gly101, Ser102, Val195, Tyr165, Arg298, Val209, Ser142, Arg233 and Gln200. Subsequently, the top...Continue Reading

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Citations

Feb 12, 2017·Applied Biochemistry and Biotechnology·Vishwanath RamatenkiUma Vuruputuri
Apr 14, 2017·Journal of Chemical Biology·Vishwanath RamatenkiUma Vuruputuri

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