همایش ملی بیوانفورماتیک ایران

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

Molecular Docking Study of Tromethamine and Its Analogues as Streptococcus mutans’s Enolase Inhibitors: A Novel Therapeutic Strategy

نویسندگان :

Kosar Feyzbakhsh¹ Hannaneh Damavandinia² 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 شهید بهشتی

کلمات کلیدی :

Streptococcus mutans،Tromethamine،Enolase،Molecular Docking

چکیده :

Introduction Streptococcus mutans is a gram-positive bacterium known to be a causative agent of dental caries and bacterial endocarditis. This bacterium proficiently converts sugars into substantial quantities of lactic acid and exhibits the capability to develop strong biofilms in the presence of sucrose (Zhang et al., 2020). Enolase, a surface-associated protein found in this bacterium, plays a crucial role in the glycolytic pathway and its pathogenesis. Although fluoride inhibits bacterial activity and plaque acid production, recent studies have demonstrated that fluoride-resistant S. mutans are widespread. Nevertheless, it has been proposed that the inhibition of Enolase is attributed to the antibacterial capacity of fluoride (Mitsuhata et al., 2014, Zhang et al., 2020). Therefore, in this study, we investigated the drug repurposing of tromethamine as an inhibitor of Streptococcus pneumoniae Enolase for inhibiting Enolase of Streptococcus mutans using molecular docking analysis. Material and Methods For this purpose, the sequence of Streptococcus mutans’s Enolase enzyme was obtained from the UniProt (Q8DTS9). The 3D structure of Enolase was predicted by the ITASSER server and refined using the GalaxyRefine server. The 3D structure of tromethamine (DrugBank ID: DB03754) and its 20 analogs were obtained from the PubChem database in SDF format. After preparing protein and ligands, molecular docking was performed using the Molegro Virtual Docker v. 6. Only the top 1 pose of each ligand was selected in Molegro Virtual Viewer v. 7, and the best ligand with the lowest energy binding was evaluated. Finally, the pharmacokinetic properties of ligands were estimated using the SwissADME database. Results and Conclusion The best ligand for Enolase was [1-Hydroxy-2-(hydroxymethyl)butan-2-yl]azanium (PubChem CID: 7058177), with a molecular weight of 120.17 g/mol and the most negative ΔGbind (-54/6212 kcal/mol). This ligand formed five hydrogen bonds with the Enolase residues, Glu375, Glu375, Ser377, Gln407, and Arg120, one electrostatic interaction with Glu375, and five steric interactions involving the Enolase residues of Arg120, Glu375, Glu375, Ser377, and Gln407. Moreover, the ADME results indicated that this ligand had a water solubility score of (LogS) 0.43, two hydrogen bond acceptors, three hydrogen bond donors, a lipophilicity score of (XLOGP3) -1.30, and a polarity score (TPSA) of 68.10. Based on the obtained results, [1-Hydroxy-2-(hydroxymethyl)butan-2-yl]azanium (PubChem CID: 7058177) demonstrated the best interaction with the lowest energy binding with Enolase, and good Druglikeness properties which it may serve as an inhibitor candidate for Enolase of Streptococcus mutans, although further in vivo and in vitro analysis are necessary.