Bitterness remains a significant sensory barrier in the formulation of nutraceutical and functional food products,particularly those enriched with polyphenols and other bioactive compounds.In this study,we applied an ...Bitterness remains a significant sensory barrier in the formulation of nutraceutical and functional food products,particularly those enriched with polyphenols and other bioactive compounds.In this study,we applied an integrative in silico approach combining molecular docking and quantum-chemical calculations(GFN-FF)to evaluate the binding affinities of 16 natural bitter compounds to three human bitter taste receptors:TAS2R14,TAS2R38,and TAS2R46.Structural models were based onсryogenic electron microscopy(cryo-EM)data and AlphaFold predictions.Binding sites were identified using DoGSite3,and ligand-receptor interactions were analyzed in terms of binding energy,interaction type,and spatial complementarity.Our results showed that compounds such as chlorogenic acid,ellagic acid,and kaempferol exhibit strong predicted affinity for TAS2R14 and TAS2R46.At the same time,TAS2R38 showed a more selective,spatially limited binding pocket.Quantum chemical calculations confirmed the docking results and provided refined energy profiles for ligand binding to local receptor fragments.The data obtained demonstrate the importance of molecular geometry in receptor binding.The data obtained highlight the importance of molecular geometry in receptor binding and indicate that understanding how bitter compounds interact with taste receptors can guide the rational selection of compounds that mask bitterness.These data enable the rational development of formulations,including those containing nutraceuticals,with improved consumer acceptability.展开更多
基金the state assignment of the Ministry of Science and Higher Education of the Russian Federation(project N◦075-15-2024-483).
文摘Bitterness remains a significant sensory barrier in the formulation of nutraceutical and functional food products,particularly those enriched with polyphenols and other bioactive compounds.In this study,we applied an integrative in silico approach combining molecular docking and quantum-chemical calculations(GFN-FF)to evaluate the binding affinities of 16 natural bitter compounds to three human bitter taste receptors:TAS2R14,TAS2R38,and TAS2R46.Structural models were based onсryogenic electron microscopy(cryo-EM)data and AlphaFold predictions.Binding sites were identified using DoGSite3,and ligand-receptor interactions were analyzed in terms of binding energy,interaction type,and spatial complementarity.Our results showed that compounds such as chlorogenic acid,ellagic acid,and kaempferol exhibit strong predicted affinity for TAS2R14 and TAS2R46.At the same time,TAS2R38 showed a more selective,spatially limited binding pocket.Quantum chemical calculations confirmed the docking results and provided refined energy profiles for ligand binding to local receptor fragments.The data obtained demonstrate the importance of molecular geometry in receptor binding.The data obtained highlight the importance of molecular geometry in receptor binding and indicate that understanding how bitter compounds interact with taste receptors can guide the rational selection of compounds that mask bitterness.These data enable the rational development of formulations,including those containing nutraceuticals,with improved consumer acceptability.
