COMPLEXES FORMED BETWEEN SWEETENERS AND BOVINE β-LACTOGLOBULIN PROTEIN: AN IN SILICO STUDY BY COMPUTATIONAL DOCKING

Sweeteners are compounds used to bring or reinforce a sweet taste to foods, reducing/eliminating the use of sugar and having anti-cariogenic and hypocaloric properties. However, the interaction of these sweeteners with proteins, such as β-lactoglobulin (β-Lg), can lead to complexes that modify the resulting perception of sweetness. Among these additives, the sulfonamides acesulfame-K (ac-K) and sodium cyclamate (c-Na), the peptide-like neotame and aspartame, and sucralose are often used. Due to their different molecular structures, they can present different intermolecular interaction patterns with β–Lg, a whey protein common in many formulations. To gain a deeper understanding of such interactions, we studied the coupling of these sweeteners’ molecules with β-Lg using computational molecular docking calculations. For the sulfonamide ac-K, 4 putative binding sites were found, highlighting site 1, in the Trp19 region, forming pi-sulfur (5.60 Å) and pi-sigma (3.87 Å) interactions and hydrogen bonding (2.19 and 2.72 Å), as well as the site 2, with alkyl (4.62Å), pi-alkyl (5.11 Å), hydrogen bond (2.34 Å) and electrostatic interactions (5.24 Å) with the residue Arg148. For c-Na, 2 putative sites were found. Site 5 had pi-alkyl interactions (4.43 Å), pi-sulfur (4.63 Å), and hydrogen bonding (2.41 Å), whereas in site 6, alkyl (4.55 and 4.76 Å) and hydrogen bonding (2.84 and 2.93 Å). Aspartame showed 3 sites, emphasizing site 8, around Asn90, Asn109, and Lys60, which showed the ligand formed 4 hydrogen bonds (2.05, 2.63, 2.64, and 2.85 Å) and 1 pi-sigma interaction (3.52 Å). Neotame had only 1 putative binding site, the region of residues between Thr4 and Thr76, where alkyl (4.51 Å), pi-sigma (3.48 Å), and hydrogen bonds (2.08 Å, 2.92 Å, 3.00 Å, and 2.71 Å) interactions were detected. Finally, for sucralose, 2 sites were identified. Site 11 formed 3 hydrogen bonds (2.66, 2.19, and 1.96 Å) with residues Thr6, Met7, and Lys8, and 2 alkyl interactions (4.29 and 3.66 Å) with residues Lys8 and Ile78. These complexes will be submitted to molecular dynamics (DM) and MM/PBSA analyses, which are expected to provide information on their temporal stability and possible conformational changes in β-Lg due to the sweeteners' complexation. Moreover, the binding ΔG will be calculated, providing a thermodynamic view of the complex formation between these food additives and the β-Lg.