Quantitative investigations of Zebrafish olfactory receptor ORA1 responsiveness to three pheromones: Microscopic and macroscopic characterizations via an advanced statistical physics treatment

In this work, an adsorption phenomenon putatively involved in the olfactory sense of phenylacetic acid, 4-chlorophenylacetic acid, and 4-methoxyphenylacetic acid pheromones in the Zebrafish olfactory receptor ORA1 was a helpful mechanism in interpreting and characterizing the olfaction process at a molecular level. Hence, the experimental dose-olfactory response curves were fitted by applying the one-layer adsorption model with a single energy (1LM1E). On one hand, the different parameters introduced in the selected model were used to microscopically study the three olfactory systems. Indeed, the fitting results showed that phenylacetic acid displayed the greatest maximum olfactory response at saturation, due to the effect of functional groups at the R4 position. The three pheromones were docked via a non-parallel orientation and the adsorption process was a multimolecular mechanism. The sizes of different binding pockets of ORA1 were determined through the estimation of the olfactory receptor site size distributions (stereographic characterization). The estimated adsorption energies, ranging from 17.340 to 21.332 kJ/mol, can be used to describe the energetic interactions between the studied pheromones and the Zebrafish ORA1 binding pockets. The spectrums of the adsorption energy distributions of phenylacetic acid, 4-chlorophenylacetic acid, and 4-methoxyphenylacetic acid, which were spread out from 10 to 32.5 kJ/mol, 5 to 30 kJ/mol, and 10 to 32.5 kJ/mol, respectively, was determined to estimate the corresponding olfactory bands (energetic characterization). On the other hand, three thermodynamic functions were estimated in order to macroscopically study the three olfactory systems.