همایش ملی بیوانفورماتیک ایران

صفحه اصلی / 4th international edition and 13th Iranian Conference on Bioinformatics

Homology modeling and molecular docking studies for discovering FlgK protein inhibitors; Helicobacter pylori flagellar subunit.

نویسندگان :

Vajiheh Eskandari¹

1- Department of Biology, Faculty of Science, University of Zanjan, Zanjan, Iran

کلمات کلیدی :

Helicobacter pylori،Molecular Docking،Natural organic compounds،Flgk

چکیده :

The flagella of the pathogens play significant roles in the initial phase of the bacterial infection process. It has been shown that FlgK is important for flagella formation and Helicobacter pylori (H. pylori), therefore deletion of the flgK flagellum, prevents normal flagellar assembly and reduces H. pylori colonization on the gastrointestinal mucosa (Gu, 2017) Two proteins, FlgK and FlgL form the hook-filament junction, therefore, the one of the best point to target Flgk, is interface area of FlgK/FlgL. With this concept, a molecular docking investigation was carried out for natural organic compounds (1000 molecules) with interface area of FlgK/FlgL. The amino acid sequences of the FlgK and FlgL were retrieved from the UniProt database (Apweiler and Bairoch, 2004) and the three-dimentional structure of the proteins were predicted using Modeller 9 & 22 software (Fiser and Sali, 2003).The Verify-3D, PROCHECK program and ProSA II web server were used for evaluation of models. GRAMM-X and ClusPro 2.0 were exploited to predict and assess the interactions between the hook-filament junction proteins FlgK and FlgL and the interaction sites were determined using the PDBePISA and Discovery Studio 4.1. The ligand-binding residues were predicted on FlgK by FTMap and COACH server. The ligand binding sites of FlgK which overlapped with the interface area of FlgK/FlgL, were selected as the target locations (V568, E572, E573, N576, A585, A586, N587, A588, K589, I598, D599 and T600) for Molecular docking study. The molecular docking were down using Autodock Vina (Trott and Olson, 2010 ) and Autodock 4 in pyRx program (Dallakyan and Olson, 2015) and the output results were evaluated using soft Discovery Studio software. The results of ligand docking assessments against FlgK, revealed that the ligands with best binding affinity scores –i.e., the most negative binding energies are observed for the compounds; Asiatic acid with Binding energy -11.5, S3899 Hederagenin with Binding energy -10.8, S3847 Panaxatriol with Binding energy -10.8, S4754 Betulin with Binding energy -10.5, Betulinic acid with Binding energy -10.5, Oleanolic acid with Binding energy -10.5, Ursolic Acid with Binding energy -10.3, Digoxin with Binding energy -10 and Enoxolone with Binding energy -9.7. Finally, this in silico study suggests that FDA approved natural organic compunds; exhibited powerful potential inhibitory against flagellar biogenesis in H. pylori.