Investigation of olfactory perception by a putative adsorption process of sotolone and abhexone on human olfactory receptor OR8D1: Statistical physics modeling and molecular docking.

In the present paper, a double layer advanced model was used to investigate the adsorption process putatively involved in the olfactory perception of sotolone and abhexone molecules on the human olfactory receptor OR8D1. The number of adsorbed molecules or the fraction of adsorbed molecule per site, n, informed that the two odorants molecules are docked on OR8D1 binding sites with mixed parallel and nonparallel anchorages. Furthermore, the estimated molar adsorption energy (-ΔE1 and -ΔE2) were inferior to 40 kJ/mol for the two adsorption systems, which confirmed the physical nature and the exothermic character of the adsorption process. In addition, stereographic characterizations of the receptor sites surface were carried out through the determination of the receptor site size distribution (RSDs) via Kelvin equation, which spread out from 0.05 to 1.5 nm. The adsorption energy distributions (AEDs) via Polayni equation show an adsorption band spectrum localized between 17 kJ/mol and 22.5 kJ/mol for sotolone and abhexone molecules respectively. A molecular docking calculation was performed. The results indicate that the binding affinities are belonging to the spectrum of the energy band of the molecules sotolone and abhexone, with values 19.66 kJ/mol and 19.24 kJ/mol.

Modeling by statistical physics and interpretation of the olfactory process of the two enantiomers 3-mercapto-2-methylbutan-1-ol and 3-mercapto-2-methylpentan-1-ol on the OR2M3 human olfactory receptor.

In the present paper, a putative adsorption process of two odorants thiols (3-mercapto-2-methylbutan-1-ol and 3-mercapto-2-methylpentan-1-ol) on the human olfactory receptor OR2M3 has been investigated via advanced models developed by a grand canonical formalism of statistical physics. For the two olfactory systems, a monolayer model with two types of energy (ML2E) has been selected to correlate with the experimental data. The physicochemical analysis of the statistical physics modeling results showed that the adsorption system of the two odorants was multimolecular. Furthermore, the molar adsorption energies were inferior to 22.7 kJ/mol, which confirmed the physisorption process of the adsorption of the two odorant thiols on OR2M3. In addition, quantitative characterizations of both odorants were determined via the olfactory receptor pore size distribution (RPSD) and the adsorption energy distribution (AED), which were spread out from 0.25 to 1.25 nm and from 5 to 35 kJ/mol, respectively. For thermodynamic characterization of the olfactory process, the adsorption entropy indicated the disorder of the adsorption systems of 3-mercapto-2-methylbutan-1-ol and 3-mercapto-2-methylpentan-1-ol on the human olfactory receptor OR2M3. Besides, the used model showed that the presence of copper ions increases the efficacy (olfactory response at saturation) of 3-mercapt-2-methylpentan-1-ol odorant activating OR2M3. The docking molecular simulation indicated that the 3-mercapto-2-methylpentan-1-ol molecule presented more binding affinities (17.15 kJ/mol) with olfactory receptor OR2M3 than 3-mercapto-2-methylbutan-1-ol (14.64 kJ/mol). On the other hand, the two estimated binding affinities of the two odorants belonged to the adsorption energies spectrum (AED) to confirm the physisorption nature of the olfactory adsorption process.

Advanced investigation of a putative adsorption process of nine non key food odorants (non-KFOs) on the broadly tuned human olfactory receptor OR2W1: Statistical physics modeling and molecular docking study.

In the present paper, statistical physics formalism was used to understand the olfactory perception via the investigation of dose-olfactory response curves of a putative adsorption process of nine non key food odorants (non-KFOs) on the broadly tuned human olfactory receptor OR2W1, in order to quantitative characterize the interactions between the nine studied non-KFOs, i. e., furfuryl sulfide, furfuryl disulfide, benzyl methyl disulfide, furfuryl methyl disulfide, benzyl methyl sulfide, 1-phenylethanethiol, benzyl mercaptan, furfuryl methyl sulfide and 3-phenylpropanol molecules and OR2W1 binding sites at a molecular level. Two advanced adsorption models have been proposed: the advanced monolayer monoenergy model (monolayer model with identical and independent olfactory receptor binding sites) (Model 1) and the advanced monolayer model with two independent types of olfactory receptor binding sites (Model 2). It was concluded that the monolayer monoenergy model was selected as the most adequate model to fit the experimental dose-olfactory response curves tabulated in literature. Actually, the numerical values of the three fitted physico-chemical parameters (RM1, n and C1) were obtained by a non-linear regression. Indeed, modeling results suggested that the number of docked non-KFOs per OR2W1 binding site n values (1.24 < n < 1.94) was always superior to 1, which indicated the non-parallel orientation of the studied odorants on the olfactory receptor and the multi-molecular adsorption mechanism. The estimated molar adsorption energy ΔEa values (ranged from 6.07 to 12.16 kJ/mol) for the nine olfactory systems confirmed the physical the exothermic characters of the adsorption process since ΔEa values were lower than 40 kJ/mol and positive. Furthermore, these estimated parameters were applied to characterize stereographically and energetically the interaction between the nine non-KFOs and OR2W1 through the determination of the human receptor binding site size distributions (RSDs) and the adsorption energy distributions (AEDs), which were spread out from 0.25 to 6.50 nm and from 0 to 22.50 kJ/mol, respectively. The docking computation between these nine non-KFOs and OR2W1 proved that the estimated binding affinities were belonged to the adsorption energies spectrum in general and the specific adsorption energy band or the molecular vibration modes limited spectrum (between 2.50 kJ/mol and 17 kJ/mol) (approximate olfactory band).

Advanced investigation of the olfactory perception of semiochemical TMT on OR5K1 and Olfr175 by statistical physics approach.

The adsorption of the trimethylthiazoline (TMT) on the human olfactory receptor OR5K1 and the mouse olfactory receptor Olfr175 was the object of the present paper. The main contribution of this work was to characterize stereographically and energetically OR5K1 and Olfr175 activated by trimethylthiazoline molecules docked on the human and the mouse olfactory binding pockets using the grand canonical ensemble in statistical physics. The experimental data and the advanced statistical physics models revealed that the adsorption of the trimethylthiazoline on the human olfactory receptor OR5K1 can be interpreted using the monolayer model with single energy, while the monolayer model with two energies described the interaction between the trimethylthiazoline molecules and the mouse olfactory receptor Olfr175. In fact, the investigated odorant was shown to be docked by a multi-docking process and non parallel orientation on OR5K1 and Olfr175 since the values of the number of TMT molecules per binding site n were superior to 1. The proposed models were applied to calculate the human and the mouse olfactory receptor binding site size distributions relative to TMT, which were spread out from 0.30 to 20 nm with a maximum at about 1.75 nm for OR5K1 and from 1 to 25 nm with a peak at about 4.25 nm for Olfr175. Furthermore, it was found from the calculated molar adsorption energies, which were lower than 11 kJ/mol, that physical adsorption process was occurred in the two olfactory systems. The adsorption energy distributions relative to TMT can be also calculated in order to understand of olfaction process in general through the determination of olfactory bands (i. e., adsorption energy distribution bands), which were situated between 0 and 10.50 kJ/mol and between 3 and 12.50 kJ/mol for OR5K1 and Olfr175, respectively. Referring to the investigation of thermodynamic functions governing the adsorption process such as the adsorption entropy, the Gibbs free enthalpy and the internal energy, it may be noted that the disorder peak of the two olfactory systems was reached when the equilibrium concentration was equal to the concentration at half saturation. In addition, the Gibbs free enthalpy and the internal energy were calculated and their negative values indicated that the adsorption process involved in the olfactory mechanism was exothermic and spontaneous nature.