Druggable sites identification in Streptococcus mutans VicRK system evaluated by catechols

Area of Science:

• Biochemistry and Molecular Biology
• Computational Drug Discovery
• Microbiology

Background:

• Dental caries is a prevalent global health issue, often linked to cariogenic dental biofilms.
• The Streptococcus mutans VicK system regulates glycosyltransferases (Gtfs), key in biofilm formation, making it a target for inhibitors.

Purpose of the Study:

• To identify potential inhibitors of the Streptococcus mutans VicK system using structure-based virtual screening and molecular dynamics simulations.
• To evaluate the binding affinity and stability of identified inhibitors.

Main Methods:

• Downloaded VicK protein structure from PDB and analyzed druggable sites (S1, S2, S3) using PockDrug and FTMap.
• Performed virtual screening of 383 catechols against VicK using AutoDock4.2.
• Conducted 200 ns Molecular Dynamics (MD) simulations and MM-PBSA analysis for binding affinity.

Main Results:

• Identified strong binding interactions of catechols with VicK kinase and phosphatase sites via hydrogen bonding, hydrophobic interactions, and π-stacking.
• Calculated optimal ligand efficiency indexes (LE, LELP, LLE, BEI).
• MD simulations confirmed stability (RMSD, RMSF) and high hydrogen bonding for peltatoside and maritimein complexes.

Conclusions:

• Catechols, particularly peltatoside and maritimein, show potential as inhibitors of exopolysaccharide synthesis.
• These findings support the development of novel anti-cariogenic and antimicrobial agents for dental biofilm management.