Abstract
•Physico-chemical interpretations were derived from musk tibetene, muscone and dihydrocivetone olfactory response curves modeling by a statistical physics treatment.•Calculation with statistical physics model was used to determine the RSDs and the AEDs.•Determination of olfaction band of musk tibetene, muscone and dihydrocivetone molecules.
An adsorption mechanism of three odorants, namely musk tibetene, muscone and dihydrocivetone, on the human musk olfactory receptor OR5AN1 has been investigated using the grand canonical ensemble in statistical physics. Experimental concentration-olfactory response curves have been fitted using two advanced models derived from statistical physics approach by numerical simulation that showed a good correlation between the advanced adsorption models and the experimental data. The adequate model, that was the monolayer adsorption model with identical and independent binding sites (MM), allowed recovering important information about the adsorption process putatively introduced in the olfactory perception by determining the maximum response at saturation (RM), the fraction or the number of captured musk molecule(s) per binding site (n) and the adsorption energy (ΔEa) by referring to the concentration at half saturation (C1), which could correspond mainly to the odorant-human olfactory receptor binding cavity interaction energy.
For the three studied olfactory systems, the adsorption energies from dissolved state in module calculated from experimental data modeling were ranged from 5.98 to 9.93 kJ/mol, which could be associated to a physisorption mechanism. The monolayer model (MM) was additionally applied to determine the human musk olfactory receptor binding site (cavity) size distribution (RSD). Indeed, musk tibetene, muscone and dihydrocivetone RSDs were spread out from 0.3 to 16 nm, from 1 nm to 16 nm and from 1 nm to 16 nm, respectively, with a maximum of order of 2.3 nm, 3.4 nm and 3 nm, respectively. In addition, the adsorption energy distribution (AED) can be also estimated for the energetic characterization to confirm the heterogeneity of the OR5AN1 surface, the physical nature of the musk tibetene/muscone/dihydrocivetone-OR5AN1 interactions and the binding of the human musk olfactory receptor OR5AN1 with the three musk odorants for a better understanding of the olfaction process in general through the determination of an olfactory band (AED band) of order of 16 kJ/mol [2–18 kJ/mol], 8 kJ/mol [2–10 kJ/mol] and 9.5 kJ/mol [3–12.5 kJ/mol] for musk tibetene, muscone and dihydrocivetone, respectively.