New insights into the docking mechanism of 4-methylphenol adsorption on cow and human olfactory receptors: Molecular docking simulation statistical physics modeling

This is the authors' abstract. We don't add key points for this paper.

A modified one-layer model with single energy was applied to microscopically and macroscopically analyze the process of docking implicated in the smell sense by applying the molecular statistical physics theory. Hence, three physicochemical parameters estimated using numerical simulation, namely the number of docked 4-methylphenol per OR9Q2 binding pocket ( n ), half-saturation concentration ( C i ), and saturation olfactory response ( R M ), were investigated. Indeed, the fitting results indicated that the cow btOR9Q2 presented by far the highest activity, displaying a tenfold increased maximum olfactory response to 4-methylphenol than the human hOR9Q2. The 4-methylphenol molecules were docked on btOR9Q2 and hOR9Q2 binding pockets with a nonparallel orientation. The interactions between the 4-mythylphenol molecules and the binding pockets of btOR9Q2 and hOR9Q2 were exothermic in nature and occurred via physical adsorption . Microscopically, it may be deduced that the statistical physics and the molecular docking investigations were complementary and presented a high level of precision for the mechanism of docking that cannot be achieved by experiments. The macroscopic interpretation of the studied olfactory systems was performed through the investigation of three thermodynamic potentials (i.e., the Gibbs free energy G , the internal energy E int , and the configurational entropy S a ), which governed the cow and human olfactory systems. Lastly, the adjusted parameters of the used model may also be applied to provide access to quantitative characterization of btOR9Q2 and hOR9Q2 by calculating the pocket size distributions (PSDs) and the distributions of the adsorption energies (AEDs).