In Silico Analysis of BMP-2 And MMP-9 Interaction with Epicatechin, Cocamide, and Theobromine from Cocoa Bean (Theobroma cacao L.) Extract for Orthodontic Movement

Background: The high prevalence of malocclusion in Indonesia (80%) necessitates orthodontic treatment involving alveolar bone remodeling regulated by Bone Morphogenetic Protein-2 (BMP-2) and Matrix Metalloproteinase-9 (MMP-9). Bioactive compounds in cocoa beans (Theobroma cacao L.), such as epicatechin, theobromine, and clovamide, may modulate these proteins, offering potential therapeutic applications. 

Objective: This in silico  study aimed to predict interactions between cocoa-derived compounds (epicatechin, theobromine, clovamide) and target proteins (BMP-2, MMP-9). 

Methods: A computational chemistry approach was employed. Ligand structures were minimized using PyRx 0.8, while protein structures (BMP-2 PDB: 6OMN; MMP-9 PDB: 5TH6) were prepared via PyMol. Molecular docking analyzed binding affinities (kcal/mol) and interaction types (hydrogen bonds, hydrophobic, van der Waals) using Discovery Studio v20. Simvastatin served as control. 

Results: Bone Morphogenetic Protein-2 (BMP-2) activation: clovamide showed the strongest affinity (-6.5 kcal/mol), near simvastatin (-6.8 kcal/mol), forming hydrogen bonds with Trp31/Tyr103 and van der Waals interactions with key residues (Met89, Leu92). MMP-9 inhibition: clovamide (-7.3 kcal/mol) and epicatechin (-6.8 kcal/mol) outperformed simvastatin (-6.3 kcal/mol), binding critical residues (Arg51, Thr96, Gly186) via hydrogen bonds and electrostatic interactions. 

Conclusion: Cocoa beans extract such a clovamide exhibits dual potential to activating BMP-2 and inhibiting MMP-9—making it a candidate for adjunctive orthodontic therapy. Further in vitro/in vivo validation is required to confirm these computational predictions.