Investigation of the adsorption mechanism of two nitro musk odorants on OR1A1: Advanced modeling and thermodynamic study

Abstract

The experimental dose-olfactory response curves of the two nitro musk odorants, such as musk tibetene and musk ambrette, on the broadly human olfactory receptor OR1A1 have been analyzed using four statistical physics models by means of the grand canonical formalism. For such a purpose, the monolayer model with one energy level and the monolayer model with two energy levels were selected to describe the adsorption mechanism of musk tibetene and musk ambrette, respectively. Indeed, three main physicochemical parameters introduced in the selected models affecting the putative adsorption phenomenon involved in the sense of smell, namely, the olfactory response at saturation, the number of nitro musk odorants per OR1A1 binding site, and the half saturation concentration related to the molar adsorption energy. Actually, the investigation of the number of nitro musk fragrances per binding site showed that musk tibetene and musk ambrette odorants were docked on OR1A1 binding sites by a non-parallel orientation and a multi-docking mechanism since the values of this stereographic parameter were higher than unity. Moreover, the selected adsorption models were used to estimate the broadly tuned human olfactory receptor site size distributions relative to musk tibetene and musk ambrette, which were spread out from 1 to 30 nm with a maximum at 4.10 nm for musk tibetene and at 3.55 nm for musk ambrette. Energetically speaking, the magnitudes of the molar adsorption energies, which were inferior to 5 kJ/mol, indicated that the two nitro musk fragrances were physisorbed on OR1A1 binding sites. Furthermore, the adsorption energy distributions, relative to the two olfactory systems, may be estimated to deeply comprehend human olfactory perception, at a molecular level, via the determination of two approximate olfactory bands through the estimation of two adsorption energy distribution bands, which were spread out from 0 to 8.50 kJ/mol for musk tibetene and from 0 to 8 kJ/mol for musk ambrette. Lastly, macroscopically speaking, three thermodynamic potentials governing the adsorption mechanism were studied. Hence, the disorder during the putative adsorption mechanism was followed via the study of the adsorption entropy. Lastly, the adsorption process introduced in the two olfactory systems was spontaneous and exothermic as it was suggested by the Gibbs free energy and the internal energy.