Ligand-Guided Homology Modelling of the Human Bitter Taste Receptor TAS2R10

Abstract

Despite low sequence identity with crystallized GPCRs, a homology model of the bitter receptor, TAS2R10 was constructed using single-template comparative modeling and refined using a combination of docking and molecular dynamic simulations. This ligand-guided strategy for model refinement resulted in an excellent correlation between the binding affinity of a chemically diverse set of known TAS2R10 bitter ligands and their docking scores with a r² value of 0.87, giving credence to the accuracy of the built homology model. A critical analysis of the binding site interactions of the bitter ligands revealed the all-encompassing nature of the TAS2R10 active site with a balanced blend of both polar as well as hydrophobic amino acids, bestowing it with promiscuity towards a large set of diverse bitter ligands. This functionally validated homology model can be used for the structure-based screening of compounds for their bitter tasting potential.