Homology Modeling and Virtual Screening to Discover Potent Inhibitors Targeting the Imidazole Glycerophosphate Dehydratase Protein in Staphylococcus xylosus

Abstract

The imidazole glycerophosphate dehydratase (IGPD) protein is a therapeutic target for herbicide discovery. It is also regarded as a possible target in <i>Staphylococcus xylosus</i> (<i>S. xylosus</i>) for solving mastitis in the dairy cow. The 3D structure of IGPD protein is essential for discovering novel inhibitors during high-throughput virtual screening. However, to date, the 3D structure of IGPD protein of <i>S. xylosus</i> has not been solved. In this study, a series of computational techniques including homology modeling, Ramachandran Plots, and Verify 3D were performed in order to construct an appropriate 3D model of IGPD protein of <i>S. xylosus</i>. Nine hits were identified from 2,500 compounds by docking studies. Then, these nine compounds were first tested <i>in vitro</i> in <i>S. xylosus</i> biofilm formation using crystal violet staining. One of the potential compounds, baicalin was shown to significantly inhibit <i>S. xylosus</i> biofilm formation. Finally, the baicalin was further evaluated, which showed better inhibition of biofilm formation capability in <i>S. xylosus</i> by scanning electron microscopy. Hence, we have predicted the structure of IGPD protein of <i>S. xylosus</i> using computational techniques. We further discovered the IGPD protein was targeted by baicalin compound which inhibited the biofilm formation in <i>S. xylosus</i>. Our findings here would provide implications for the further development of novel IGPD inhibitors for the treatment of dairy mastitis.