Assessment of Acetic Acid Interaction with MMP-8 and MMP-9: Implications for Dentin Matrix Degradation in Early Childhood Caries - An in silico study

Abstract

Background: Early childhood caries (ECC) is a multifactorial disease characterized by progressive demineralization and degradation of dental hard tissues. Acetic acid, a metabolic by-product of cariogenic bacteria, contributes to the acidic environment associated with caries progression. Matrix metalloproteinases (MMPs), particularly MMP-8 and MMP-9, play crucial roles in dentin collagen degradation following demineralization. Aim: To evaluate the molecular interaction of acetic acid with MMP-8 and MMP-9 using an in silico molecular docking approach and assess its potential implications in dentin matrix degradation associated with ECC. Materials and Methods: Three-dimensional structures of MMP-8 (PDB ID: 1BZS) and MMP-9 (PDB ID: 1GKC) were retrieved from the Protein Data Bank. Acetic acid (PubChem CID: 176) was used as the ligand. Molecular docking was performed using PyRx integrated with AutoDock Vina, and protein–ligand interactions were analyzed using BIOVIA Discovery Studio Visualizer. Results: Acetic acid demonstrated weak binding affinities toward MMP-8 and MMP-9, with docking scores of −3.2 kcal/mol and −3.1 kcal/mol, respectively. MMP-8 exhibited hydrogen bonding, aromatic interactions, and zinc associated contacts, whereas MMP-9 interactions were predominantly mediated through van der Waals forces. Conclusion: Acetic acid showed limited direct interaction with MMP-8 and MMP-9. Its contribution to ECC may be primarily indirect through maintenance of an acidic microenvironment that promotes dentin demineralization and facilitates MMP-mediated collagen degradation..