Targeting Matrix Metalloproteinase-3 for Dental Caries Prevention Using Herbal Isolates: MMP3 Inhibition by Cinnamic...

Area of Science:

• Biochemistry
• Oral Biology
• Computational Chemistry

Background:

• Dental caries is a significant global health issue, ranking high among prevalent diseases.
• Matrix metalloproteinase-3 (MMP3) in demineralized dentin degrades proteoglycans, exposing collagen and accelerating demineralization.
• Inhibiting MMP3 activity presents a potential strategy for dental caries prevention.

Purpose of the Study:

• To evaluate the binding affinity of 20 cinnamic acid derivatives to the MMP3 catalytic cleft.
• To assess the stability of MMP3 complexes with top-ranked inhibitors using molecular dynamics simulations.
• To identify potent MMP3 inhibitors for potential dental caries prevention.

Main Methods:

• Docking simulations using AutoDock 4.0 to predict binding affinity of cinnamic acid derivatives to MMP3.
• Molecular dynamics simulations over 100 ns to analyze the stability of MMP3 and its complexes.
• Analysis of binding free energy (ΔGbinding) and inhibition constants (Ki).

Main Results:

• Four cinnamic acid derivatives exhibited binding scores below -10 kcal/mol.
• Cynarin demonstrated the highest potency as an MMP3 inhibitor, with a ΔGbinding of -15.57 kcal/mol and Ki of 3.83 pM.
• The MMP3-cynarin complex remained stable during a 50 ns simulation, indicating a robust interaction.

Conclusions:

• Cynarin, chlorogenic acid, rosmarinic acid, and cinnamyl caffeate are identified as promising MMP3 inhibitors.
• These compounds hold potential as a novel preventive strategy against dental caries.
• Targeting MMP3 with specific cinnamic acid derivatives offers a new avenue for caries management.