• Homology modeling and molecular docking to identify potent inhibitors targeting FglK protein; Helicobacter pylori flagellar subunit.
  • Vajiheh Eskandari,1,*
    1. Department of Biology, Faculty of Science, University of Zanjan, Zanjan, Iran


  • Introduction: The flagella play an important role in the initial phase of the infection process of many pathogenic bacteria. It has been shown that FlgK is important for flagella formation and motility of H pylori, therefore deletion of the flgK protein, prevents normal flagellar assembly and reduces the colonization of the gastrointestinal mucosa. FlgK along with FlgL form the hook-filament junction, Therefore, the one of the best point to target Flgk, is where it connects and interacts with FlgL. With this concept, a molecular docking analysis for vitamins and their derivatives (47 molecules) with interface area of FlgK/FlgL was carried out.
  • Methods: The amino acid sequences of the FlgK and FlgL were extracted from the UniProt database and the 3D-structure of the proteins were predicted using Modeller 9 & 22 software .The models evaluation were done using Verify-3D, PROCHECK program andProSA II web server. GRAMM-X and ClusPro 2.0 were used to predict and assess the interactions between the hook-filament junction proteins FlgK and FlgL and area of interaction were determined using the PDBePISA and Discovery Studio 4.1. The ligand-binding residues were predicted on FlgK by COACH and FTMap server. 47 FDA approved vitamins were collected from Selleckchem Inc web site. Then, the ligands were evaluated as inhibitors on interface residues of FlgK/FlgL proteins by Autodock Vina and Autodock 4 in pyrx program and AutoDock Vina software, and the output results were evaluated by Discovery Studio software.
  • Results: The ligand binding sites of FlgK that overlapped with the interaction site of these FlgK and FlgL, were selected as the target sites (V568, E572, E573, N576, A585, A586, N587, A588, K589, I598, D599 and T600) for docking. The results of molecular docking indicate that the ligands with best binding scores –i.e., the most negative binding energies are observed for the compounds; Vitamin B12 with Binding energy -12.8, Ergosterol with Binding energy -10.5, Calcipotriene with Binding energy -9.6, Trolox with Binding energy -9.6, Doxercalciferol with Binding energy -9.4, Vitamin D3 with Binding energy -9.0, Calcifediol with Binding energy -8.8, Riboflavin (Vitamin B2) with Binding energy -8.7 and Dibenzoyl Thiamine (Bentiamin) with Binding energy -8.
  • Conclusion: This in silico study suggests that FDA approved vitamins Vitamin B12, Ergostero, Calcipotriene, Trolox, Doxercalciferol, Vitamin D3, Calcifediol, Riboflavin and Dibenzoyl Thiamine could serve as potential inhibitors against flagellar biogenesis in Helicobacter pylori.
  • Keywords: Molecular Docking, Helicobacter pylori, FlgK and Vitamins