This research work is a contribution to understand the olfaction mechanism at a molecular level of vanillin, ethyl vanillin, coumarin and quinoline molecules using a modeling of a putative adsorption process by analytical model established by statistical physics formalism.A statistical physics modeling using the monolayer model with identical and independent binding sites of the responses of the two human olfactory receptors OR10G4 and OR2B11 showed that vanillin and quinoline were adsorbed with a mixed non-parallel and parallel orientation on OR10G4 and on OR2B11, respectively. However, ethyl vanillin and coumarin were anchored with a total non-parallel orientation. The adsorption energy values collected from data analysis, which were ranged from 12.51 to 20.91 kJ/mol, confirmed that the adsorption of vanillin and ethyl vanillin on OR10G4 and the adsorption of coumarin and quinoline on OR2B11were exothermic and were based on physical interactions.Furthermore, the dose-olfactory response curves of vanillin, ethyl vanillin, coumarin and quinoline provided access to OR10G4 and OR2B11 steric characterization via the calculation of the studied olfactory receptors site size distributions (RSDs). Indeed, vanillin, ethyl vanillin, coumarin and quinoline RSDs are spread from 0.3 to 12 nm, from 0.5 to 12 nm, from 0.40 to 12 nm and from 0.14 to 12 nm, respectively, with a maximum at 1.55 nm, 2.11 nm, 2.50 and 1.13 nm, respectively.Lastly, the physico-chemical model parameters can be used for the energetic characterization to confirm the physical nature of the vanillin/ethyl vanillin-OR10G4 and the coumarin/quinoline-OR2B11 interactions and to determine an olfactory band of order of 12 kJ/mol [11–23 kJ/mol], 10 kJ/mol [14–24 kJ/mol], 7 kJ/mol [9–16 kJ/mol], 15 kJ/mol [13–28 kJ/mol] for vanillin, ethyl vanillin, coumarin and quinoline, respectively, through the determination of the adsorption energy distributions (AEDs).