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

Area of Science:

• * Pharmacology
• * Computational Chemistry
• * Biophysics

Background:

• * The human bitter taste receptor family (T2Rs) plays a crucial role in detecting diverse bitter compounds.
• * Understanding the molecular mechanisms of bitter taste perception is vital for drug development and food science.
• * Previous research has focused on identifying T2R agonists, but detailed interaction analyses are ongoing.

Purpose of the Study:

• * To investigate the human-like taste response of chloroquine, denatonium, and saccharin on T2R receptors.
• * To quantify intermolecular interactions and binding affinities using statistical physics and molecular docking.
• * To elucidate the stability and interaction types of these bitter molecules at a quantum chemical level.

Main Methods:

• * Statistical physics approach to fit concentration-taste response curves and estimate model parameters (R_M, n, C_1/2).
• * Molecular docking simulations to determine binding affinities with specific human T2R receptor sites (T₂R₁₀ and T₂R₃₁).
• * Quantum chemical calculations including DFT/B3LYP/6-311 G(d, p), Atoms in Molecules (AIM), NCI, and Natural Bond Orbital (NBO) analyses.

Main Results:

• * Estimated model parameters (R_M, n, C_1/2) and determined transduction coefficient (α) for the three bitter molecules.
• * Established a common gustatory band for bitter tastes with adhesive energies ranging from 2.5-22.5 kJ mol⁻¹.
• * Denatonium showed stronger binding affinity (28.87 kJ/mol) to T₂R₁₀ than chloroquine (26.78 kJ/mol), while saccharin bound to T₂R₃₁ (23.85 kJ/mol).
• * NBO and NCI analyses confirmed the significant stability of the molecules and identified Van der Waals forces and steric effects.

Conclusions:

• * The study provides a comprehensive theoretical framework for understanding bitter taste perception at the molecular level.
• * Findings highlight the distinct binding interactions of chloroquine, denatonium, and saccharin with different T2R receptor subtypes.
• * The research offers valuable data for designing novel bitter taste modulators and understanding chemosensory processes.