User:KushioRibeiro/Docking theory of olfaction



The docking theory of olfaction proposes that the smell of an odorant molecule is due to a range of weak non-covalent interactions between the odorant [a ligand] and one or more G-protein-coupled odorant receptors (found in the nasal epithelium). These include intermolecular forces, such as dipole-dipole and Van der Waals interactions, as well as hydrogen bonding. More specific proposed interactions include metal-ion, ion-ion, cation-pi and pi-stacking. Interactions can be influenced by the odorant's conformation, as well as the hydrophobic effect.

While this theory of odorant recognition has previously been described as the shape theory of olfaction, which primarily considers molecular shape and size, this earlier model is oversimplified, since two odorants may have similar shapes and sizes but are subject to different intermolecular forces and therefore activate different combinations of odorant receptors, allowing them to be distinguished as different smells by the brain. Other names for the model, such as “lock and key” and "hand in glove", are also misnomers: there are only 396 unique olfactory receptors and too many distinguishable smells for a one-to-one correlation between an odorant and a receptor.

Since olfactory receptors have not yet been successfully crystalized, the docking theory of olfaction relies on the known properties of other G-protein coupled receptors that have been crystalized to produce a likely olfactory receptor model. Simpler odorant-receptor binding models have been developed into more nuanced ideas which consider the distortion of flexible molecules so as to form optimal interactions with binding partners. These modifications help the model to conform better to what is known of the molecular docking of non-olfactory G-protein coupled receptors.

Sources:

C. Sell, Chemistry and the Sense of Smell, John Wiley and sons, Hoboken, NJ, 2014

A. Manglik, T. Kim, M. Masureel, C. Altenbach, Z. Yang, D. Hilger, M. Lerch, T. Kobilka, F. Thian, W. Hubbell, R. Prosser and B. Kobilka1, Cell. 161 (2015), p.1101.

L. Turin and F. Yoshii, Handbook of Olfaction and Gustation, 2nd ed., CRC Press Boca, Boca Raton, FL, 2003, p.275

Hoehn, Ross D., et al. “Status of the Vibrational Theory of Olfaction.” Frontiers in Physics, vol. 6, 2018, https://doi.org/10.3389/fphy.2018.00025.