Interaction mechanism of flavonoids and bovine β-lactoglobulin: Experimental and molecular modelling studies

Abstract In this study, the quantitative structure-affinity relationship of 28 flavonoids with bovine β-lactoglobulin (β-lg) was investigated based on experimental and theoretical methods. The binding constants (Ka) of these flavonoids with β-lg were systematically compared by spectrofluorimetry, and a multivariate linear model (R2 = 0.8769, Q2 = 0.7963) was established that could explain the effect of the structure parameters of flavonoids on their affinity (lgKa) for β-lg. Then, the underlying interaction mechanism was further clarified with myricetin and baicalin as representative flavonoids. Thermodynamic analysis showed that hydrogen bonds and van der Waals force played the main roles in maintaining the complexes, which was consistent with the independent gradient model (IGM) and the MM/PBSA binding free energy results. The redshift of the maximum emission peak of tryptophan residues in the synchronous fluorescence was attributed to the interaction of myricetin or baicalin with Trp19 of β-lg, according to the root mean square fluctuation (RMSF) results.