همایش ملی بیوانفورماتیک ایران

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

The inquiry of possible new candidates of inhibitors for Type IV pili of Neisseria gonorrhoeae using Molecular Docking analysis

نویسندگان :

Hannaneh Damavandinia¹ Kosar Feyzbakhsh² Zahra Golshahi³ Elnaz Afshari⁴

1- دانشگاه آزاد اسلامی واحد تهران مرکزی 2- دانشگاه آزاد اسلامی واحد تهران مرکزی 3- دانشگاه آزاد اسلامی واحد تهران مرکزی 4- دانشگاه آزاد اسلامی واحد تهران مرکزی

کلمات کلیدی :

Molecular Docking،Neisseria gonorrhoeae،Type IV pilin،ADME

چکیده :

Introduction There are several complications in women associated with the Neisseria gonorrhoeae infection, such as infertility, cervicitis, ectopic pregnancy, and urethritis, which is a common sexually transmitted infection worldwide (Vaezzadeh et al., 2023). One of the main virulence factors of Neisseria gonorrhoeae is type IV pili, which is responsible for the adhesion, mobility, and pathogenesis of this bacterium (Jacobsen et al., 2020). The rising prevalence of multi-drug resistant Neisseria strains necessitates the exploration of alternative strategies, such as inhibiting this virulence factor and the bacterium's ability to adhere to host cells. This approach presents a promising avenue for the prevention of diseases associated with this pathogen. Therefore, in this study, we aimed to identify the most potent inhibitory ligand for the pili as a potential drug candidate through molecular docking analysis. Material and Methods The 3D structure of the type IV pilin of Neisseria gonorrhoeae was extracted from the RCSB PDB database (PDB ID: 2HI2). The inhibitory ligand of pilin, methyl (2S)-2-amino-3-phenylpropanoate (methyl L-phenylalaninate) with PubchemCID 736234, and a total of its 20 analogs was retrieved from the PubChem database in SDF format. After preparing the protein and its ligands by eliminating the ligand and water from the protein, lowering the energy level, and adding electric charges and hydrogen atoms, molecular docking was conducted using Virtual Docker Molegro v. 6. Subsequently, the best interaction with the lowest energy binding was analyzed using Molegro Molecular Viewer software. Finally, the pharmacokinetic properties of the ligand were investigated using the SwissADME server. Results and Conclusion Among all the inhibitory ligands of pilin, the best ligand was (2S)-N-(3-fluorophenyl)-2-(3-phenoxyphenyl)-1,3-thiazolidine-3-carboxamide with the molecular weight of 394.12 g/mol, and binding energy of -71.2257 kcal/mol. This ligand formed one Hydrogen bond with Arg152, along with 2 steric interactions involving Arg 152 and Gln 123 residues. The ADME results demonstrated a water solubility score (LogS) of -4.965, the hydrophilic score (LogP) of 4.029, the polarity score (TPSA) of 41.57, and in conclusion the hydrogen bond donors of 4 and hydrogen bond acceptor of 1. Based on the obtained results, (2S)-N-(3-fluorophenyl)-2-(3-phenoxyphenyl)-1,3-thiazolidine-3-carboxamide (PubChem CID: 1025301) demonstrated the best interaction with the lowest energy binding with type IV pilin, and good Druglikeness properties which it may serve as an inhibitor candidate for type IV pilin of Neisseria gonorrhoeae, although further in vivo and in vitro analysis are necessary.