In silico Prediction and Docking of Tertiary Structure of LuxI, an Inducer Synthase of Vibrio fischeri

Background: LuxI is a component of the quorum sensing signaling pathway in Vibrio fischeri responsible for the inducer synthesis that is essential for bioluminescence. Methods: Homology modeling of LuxI was carried out using Phyre۲ and refined with the GalaxyWEB server. Five models were generated and evaluated by ERRAT, ANOLEA, QMEAN۶, and Procheck. Results: Five refined models were generated by the GalaxyWEB server, with Model ۴ having the greatest quality based on the QMEAN۶ score of ۰.۷۳۲. ERRAT analysis revealed an overall quality of ۹۸.۹%, while the overall quality of the initial model was ۵۴%. The mean force potential energy, as analyzed by ANOLEA, were better compared to the initial model. Sterochemical quality estimation by Procheck showed that the refined Model ۴ had a reliable structure, and was therefore submitted to the protein model database. Drug Discovery Workbench V.۲ was used to screen ۲۷۰۰ experimental compounds from the DrugBank database to identify inhibitors that can bind to the active site between amino acids ۲۴ and ۱۱۰. Ten compounds with high negative scores were selected as the best in binding. Conclusion: The model produced, and the predicted acteyltransferase binding site, could be useful in modeling homologous sequences from other microorganisms and the design of new antimicrobials.

Keywords:

Docking , Homology modeling , LuxI , Quorum sensing