The Interaction of Polyphenol Flavonoids with β-lactoglobulin: Molecular Docking and Molecular Dynamics Simulation Studies

The interaction of quercetin, quercitrin, and rutin, as natural polyphenolic compounds, with β-lactoglobulin (BLG) using molecular docking and molecular dynamics simulation methods was examined. Molecular docking studies showed that quercetin and quercitrin were bounded to the internal cavity of protein, while rutin was bounded to the entrance of the cavity because of its large structural volume. It was found that there were one-, three-, and four-hydrogen bond interactions between BLG and quercetin, quercitrin, and rutin respectively. This showed that with an increase in the number of OH groups in the flavonoid structure, there was an increase in the number of hydrogen bond interactions. The binding constants for the binding of quercetin, quercitrin, and rutin to BLG were 1.2 × 106, 1.9 × 106, and 7.4 × 104 M−1 respectively. The results of molecular dynamics simulation showed that the root mean square deviation (RMSD) of non-liganded BLG and BLG–ligand complexes reached equilibration after 3500 ps. The study of the radius of gyration revealed that BLG and BLG–ligand complexes were stabilized around 2500 ps, and unlike the two other complexes, there was no conformational change for BLG–quercetin. Finally, analyzing the RMS fluctuations suggested that the structure of the ligand binding site remained approximately rigid during simulation.