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. 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 mutants are widespread. Nevertheless, it has been proposed that the inhibition of
Enolase is attributed to the antibacterial capacity of fluoride. 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. For this purpose, the sequence of Streptococcus mutans’s
Enolase enzyme was obtained from the UniProt (Q۸DTS۹). The ۳D structure of
Enolase was predicted by the ITASSER server and refined using the GalaxyRefine server. The ۳D structure of tromethamine (DrugBank ID: DB۰۳۷۵۴) and its ۲۰ 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. ۶. Only the top ۱ pose of each ligand was selected in Molegro Virtual Viewer v. ۷, and the best ligand with the lowest energy binding was evaluated. Finally, the pharmacokinetic properties of ligands were estimated using the SwissADME database. The best ligand for
Enolase was
[۱-Hydroxy-۲-(hydroxymethyl)butan-۲-yl]azanium (PubChem CID: ۷۰۵۸۱۷۷), with a molecular weight of ۱۲۰.۱۷ g/mol and the most negative ΔGbind (-۵۴.۶۲۱۲ kcal/mol). This ligand formed five hydrogen bonds with the
Enolase residues, Glu۳۷۵, Ser۳۷۷, Gln۴۰۷, and Arg۱۲۰, one electrostatic interaction with Glu۳۷۵, and five steric interactions involving the
Enolase residues of Arg۱۲۰, Glu۳۷۵, Ser۳۷۷, and Gln۴۰۷. Moreover, the ADME results indicated that this ligand had a water solubility score of (LogS) ۰.۴۳, two hydrogen bond acceptors, three hydrogen bond donors, a lipophilicity score of (XLOGP۳) -۱.۳۰, and a polarity score (TPSA) of ۶۸.۱۰. Based on the obtained results,
[۱-Hydroxy-۲-(hydroxymethyl)butan-۲-yl]azanium (PubChem CID: ۷۰۵۸۱۷۷) 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.
