Evaluation of Bronchial Receptors with Concentration-Response Curves, Bitterness Assessment, and Computer Simulations

This research aims to explore the human-like taste response of three bitter molecules (chloroquine, denatonium, and saccharin) on the human bronchi receptor T2R agonist using a statistical physics approach. By fitting the concentration-taste response curves, we estimate three model parameters (R_M, n, C_1/2) to assess the intermolecular interactions with T2R receptor sites. In addition, the transduction coefficient (α) of the three tasting molecules has been determined. This analysis provides valuable insights into the binding energy spectrum (AES) and establishes a common gustatory band for the bitter tastes, with adhesive energies distributed over a relatively wide range (2.5-22.5 kJ mol⁻¹). In addition, molecular docking simulations were conducted, revealing that denatonium exhibits stronger binding affinities (28.87 kJ/mol) with the T₂R₁₀ human taste receptor site compared to chloroquine (26.78 kJ/mol). Conversely, saccharin displayed a binding affinity of approximately 23.85 kJ/mol with the binding pocket of the T₂R₃₁ ion channel receptors. This three molecules undergoes theoretical analysis using the DFT/B3LYP/6-311 G(d, p) basis set to determine its frontier orbital features and stability. The type and strength of interactions were identified using the topological parameters of the "Atoms in Molecules" (AIM) method, NCI analysis was used to study intra- and intermolecular noncovalent interactions within a molecular system, as well as natural bond orbital (NBO) analysis. NBO analyses indicate that all three tasting molecules exhibits significant stability. NCI interaction analyses indicate that Van der Waals forces and steric effects are observed in the three tasting molecules. 3D shaded potential surface revealed a projection of LOL examination and the electron localization function (ELF) indicated that an area of electron depletion is observed in the three tasting molecules.