Integrated In Silico Discovery of the MMP9-Binding Phytochemicals from Ageratum conyzoides Using Molecular Docking,...

Matrix metalloproteinase-9 (MMP9) is a zinc-dependent endopeptidase, it remodels extracellular matrix and is implicated in chronic inflammation and cancer development. Despite their therapeutic potential, synthetic MMP inhibitors have poor selectivity and dose-limiting toxicities, highlighting the need for safer modulators. This study used a comprehensive in silico framework to identify MMP9-binding phytochemicals in Ageratum conyzoides. The IMPPAT database yielded 507 phytochemicals for sequential pharmacokinetic, drug-likeness, and toxicity screening utilizing SwissADME, MolSoft, and ProTox-III. Molecular docking simulation was performed on 48 non-toxic chemicals after ADMET filtering. The best docking scores were found for (2Z,6Z)-Farnesyl acetate, Phytol, and Palmitic acid. Molecular docking simulations assessed time-dependent stability of these complexes using backbone RMSD, residue-wise RMSF, radius of gyration, and solvent-accessible surface area studies. Compared to the palmitic acid complexes, MMP9-(2Z,6Z)-Farnesyl acetate and MMP9-Phytol complexes had better structural stability, decreased active-site flexibility, and conserved global compactness in MD simulations. The MM-GBSA binding free energy calculations showed ΔG_bind values of -37.8 to -26.1 kcal/mol, with van der Waals interactions providing the main positive contributions. These findings suggest that (2Z,6Z)-Farnesyl acetate and Phytol are potential MMP9-interacting phytochemicals and offer a computational framework for experimental confirmation.