Computational Exploration of Advantame Binding to Human Serum Albumin

Advantame is an ultra-high-intensity, non-caloric sweetener derived from aspartame and widely incorporated into food and beverage formulations due to its exceptional sweetness potency and thermal stability. Understanding its interaction with human serum albumin (HSA)—the primary transport protein in blood—is essential for predicting its pharmacokinetic behavior, distribution, and potential biological implications. In this study, molecular docking simulations were conducted to elucidate the binding mechanism of advantame with HSA. The crystal structure of HSA (PDB ID: ۱BMO) was prepared using AutoDock Vina and MGL Tools, while the optimized ۳D structure of advantame was retrieved from PubChem and converted into PDBQT format for docking. Among the ۲۰ generated docking poses, the most energetically favorable conformation positioned advantame within subdomain IIA (Sudlow’s Site I) of HSA. Interaction analysis using BIOVIA Discovery Studio revealed that advantame forms three hydrogen bonds with residues ARG۲۲۲, VAL۲۹۳, and ALA۲۱۵, alongside a π–cation interaction with ARG۲۱۸ and a hydrophobic π–alkyl interaction involving LYS۱۹۵. These interactions collectively support the formation of a stable ligand–protein complex, consistent with the mixed polar–hydrophobic environment characteristic of Sudlow’s Site I. The predicted binding free energy (−۲۹.۷۰ kJ·mol⁻¹) further indicates a favorable and moderately strong interaction. Overall, this study provides detailed structural insights into the interaction of advantame with HSA, highlighting the central role of hydrogen bonding, electrostatic forces, and hydrophobic interactions in stabilizing the complex. These findings contribute to a deeper understanding of the potential transport, bioavailability, and physiological behavior of advantame when used as a high-intensity sweetener in food applications

کلیدواژه ها:

Advantame ، Sweeteners ، HSA ، Docking Investigation