Mimicking the Gas-Phase to Transport Odorants through the Nasal Mucus: Functional Insights into Odorant Binding Proteins

TL;DR

This study uses computational methods to show how odorant binding proteins facilitate odorant transport from the gas phase to the nasal mucus by lowering energy barriers, providing insights into olfactory mechanisms.

Contribution

It offers a molecular-level explanation of OBPs' role in odorant transport, highlighting the importance of conformational dynamics in gas-phase odorant binding.

Findings

Carvone's conformational space in pOBP resembles the gas phase more than the aqueous phase.

pOBP reduces the free energy barrier for odorant uptake.

Insights support development of biomimetic sensors for artificial noses.

Abstract

Mammalian odorant binding proteins (OBPs) have long been suggested to transport hydrophobic odorant molecules through the aqueous environment of the nasal mucus. While the function of OBPs as odorant transporters is supported by their hydrophobic beta-barrel structure, no rationale has been provided on why and how these proteins facilitate the uptake of odorants from the gas phase. Here, a multi-scale computational approach validated through available high-resolution spectroscopy experiments reveals that the conformational space explored by carvone inside the binding cavity of porcine OBP (pOBP) is much closer to the gas than the aqueous phase, and that pOBP effectively manages to transport odorants by lowering the free energy barrier of odorant uptake. Understanding such perireceptor events is crucial to fully unravel the molecular processes underlying the olfactory sense, and move towards the development of protein-based biomimetic sensor units that can serve as artificial noses.