Monascus Pigments as Natural Inhibitors of E۶AP: An Integrated Molecular Docking and Dynamics Study

Human papillomavirus (HPV)–induced carcinogenesis is driven in part by the interaction between the viral E۶ protein and the E۶-associated protein (E۶AP), which mediates the degradation of the tumor suppressor p۵۳. This study investigates the potential of Monascus-derived pigments as natural inhibitors of E۶AP using integrated in silico approaches. Pigments were evaluated through molecular docking, pharmacokinetic screening, toxicity prediction, and ۱۰۰-ns molecular dynamics simulations to assess their suitability as anticancer candidates. Docking analyses revealed strong binding affinities for ankaflavin, monascin, monascuspiloin, and monascopyridine derivatives, supported by stable hydrogen bonding and hydrophobic interactions with key E۶AP residues. ADMET screening indicated favorable drug-likeness profiles and low predicted toxicity for several pigments. Molecular dynamics simulations confirmed stable ligand–receptor complexes with low RMSD values, consistent RMSF patterns, and favorable MM-GBSA/MM-PBSA binding energies, suggesting robust inhibitory potential. These findings highlight the capacity of Monascus pigments to disrupt E۶AP-mediated pathways implicated in HPV-driven malignancy. The results provide a strong rationale for advancing these pigments into experimental studies aimed at restoring p۵۳ function and evaluating their anticancer effects. This study identifies novel natural product candidates with promising relevance for HPV-associated cancer therapeutics.

کلیدواژه ها:

Monascus pigments ، E۶AP inhibition ، Molecular docking ، Molecular Dynamics Simulation ، HPV-associated cancer ، p۵۳ restoration