INVIVO TOXICITY AND IN SILICO DOCKING STUDIES OF AH11 PEPTIDE WITH GLUCANSUCRASE OF STREPTOCOCCUS MUTANS
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Keywords
Dental caries; Streptococcus mutans; glucansucrase; antimicrobial peptide; AH11; molecular docking; zebrafish; in vivo toxicity.
Abstract
Background: Streptococcus mutans is the primary etiological agent of dental caries, primarily through the action of glucansucrases (glucosyltransferases) that synthesize extracellular polysaccharides, enabling biofilm formation and tooth demineralization. The rise of multidrug‑resistant bacteria necessitates novel, targeted antimicrobial strategies. Peptide‑based agents offer promise due to their specificity and low toxicity. AH11 is a novel peptide composed of alanine, arginine, valine, tryptophan, phenylalanine, serine, leucine, and glycine.
Objective: To evaluate the in silico binding affinity of AH11 with S. mutans glucansucrase and to assess its in vivo toxicity using zebrafish larvae.
Methods: AH11 was analyzed using ToxinPred (toxicity prediction), PeptideRanker (bioactivity score), Peptide Calculator (physicochemical properties), and helical wheel diagram (hydrophobicity). Molecular docking with glucansucrase was performed using HPEPDOCK. For in vivo toxicity, zebrafish larvae (72 hpf) were exposed to two concentrations of AH11 (10 µM and 50 µM) and compared to control and amoxicillin (50 µM) for 72 hours. Survival, heart rate, and morphological deformities were recorded in triplicates. Statistical analysis used one‑way ANOVA (p < 0.05).
Results: ToxinPred classified AH11 as non‑toxic. PeptideRanker gave a score of 0.79, indicating high bioactivity. Net charge was close to +1, but helical wheel analysis showed increased hydrophobicity and poor water solubility. Molecular docking revealed a strong binding affinity of −135 kcal/mol with glucansucrase. In zebrafish, AH11 treated larvae showed 98% survival with no decrease in heart rate or structural deformities, whereas amoxicillin showed only 50% survival. The difference was statistically significant (p < 0.05).
Conclusion: AH11 exhibits high binding affinity to S. mutans glucansucrase and an excellent safety profile in vivo, with nearly 98% survival in zebrafish and no observable toxicity. This novel peptide is a promising candidate for targeted anti‑caries therapy.
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Rakshitha V S
Undergraduate Student Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences (SIMATS), Chennai, Tamil Nadu – 600077 India.
Gayathri Devi. R
Assistant Professor,Department of Physiology, Saveetha Dental college, Saveetha Institute of Medical and Technical Science (SIMATS) Saveetha University, Chennai, India
Selvaraj J
Associate Professor, Department of Biochemistry,Saveetha Dental college,Saveetha Institute of Medical and Technical Science (SIMATS) Saveetha University, Chennai, India
A. Jothi Priya
Assistant Professor, Department of Physiology, Saveetha Dental college, Saveetha Institute of Medical and Technical Science (SIMATS)
