Understanding the adsorption mechanism of geosmin, linalool, and o-cresol on Machilis hrabei olfactory receptor MhOR5 via statistical physics modeling and molecular docking simulation.

Context: This article suggests that the olfaction process can be simplified to an adsorption mechanism by utilizing the Machilis hrabei olfactory receptor MhOR5 as a biological adsorbent. The odorant molecules such as geosmin, linalool, and o-cresol were used as adsorbates. The aim of the present study is to provide new insights into the docking process of the tested odorants on MhOR5 using numerical simulation via an advanced statistical physics model to fit the corresponding response curves.

Methods: In the present work, an advanced theory based on statistical physics formalism is applied to understand and analyze the experimental dose-olfactory response curves of three odorant molecules on the Machilis hrabei olfactory receptor. Indeed, a monolayer model with four energy levels developed using the grand canonical ensemble was successfully applied to analyze the adsorption mechanism of geosmin, linalool, and o-cresol on MhOR5 through the interpretation of the different fitted parameters. Stereographically, it was found that geosmin, linalool, and o-cresol molecules were docked on MhOR5 binding pockets with nonparallel orientations (multi-molecular process) since all the numbers of the studied odorants adsorbed on one binding pocket were superior to 1. Energetically, the values of the molar adsorption energies ΔE (i = 1, 2, 3, and 4) related to the four types of binding pockets (varied between 6.18 and 18.43 kJ/mol) demonstrated that the three odorants were exothermically and physically docked on MhOR5 since all values of ΔE were positive and inferior to 40 kJ/mol. The proposed model may also be applied to calculate and interpret two thermodynamic potentials: the internal energy E and adsorption entropy S. Additionally, the physicochemical parameters may be used to stereographically and energetically characterize the heterogeneity of the insect MhOR5 surface. The docking simulation results demonstrated that the estimated binding affinities or energy score values (varied between 6.27 and 18.40 kJ/mol) were slightly similar to molar adsorption energy values and were included in the adsorption energy bands of the three adsorption energy distributions (AEDs).