Verification of the interaction between human bitter taste receptor T2R46 and polyphenols; Computational chemistry approach
Takafumi Shimizu, Taiki Fushimi, Rio Ohno, Yasuyuki Fujii, Kenta Aso, U. Jacobs, Osamu Nureki, Yoshitomo Suhara, Vittorio Calabrese, Naomi Osakabe
Abstract
Recent studies have indicated that the activation of bitter taste receptors (T2R) expressed in gastrointestinal secretory cells has a regulatory effect on the secretion of gastrointestinal hormones. Polyphenols are known to be ingested at a daily intake of 5 g or more and commonly have a bitter taste. Consequently, the interaction between the bitter taste receptor T2R46 and 490 polyphenols was investigated using in silico simulation techniques. It was demonstrated that W88 3.32 and E265 7.39 play a pivotal role in the recognition of polyphenols and known ligands by T2R46, with frequent interactions observed, particularly with flavonoids. The results of the quantitative structure-activity relationship (QSAR) analysis demonstrated a high degree of correlation (R 2 =0.9359) between polyphenols and T2R46 in a model that incorporated molecular interaction field regions and branching scales. Furthermore, known ligands were also found to fit this model (R 2 =0.9155). These findings suggest that polyphenols may act as T2R46 ligands. • Interactions between T2R46 and 490 polyphenols were investigated in silico. • Molecular docking suggests that most polyphenols bind to T2R46. • Many flavonoids showed similar interactions to well-known T2R46 ligands. • QSAR analysis suggested relationships between binding energy score and molecular structure. • Interaction field area and molecular branching are crucial for T2R46 binding.