How Far Does a Receptor Influence Vibrational Properties of an Odorant?

Anna Reese,Nanna Holmgaard List,Ilia A Solov’Yov,Jacob Kongsted,Efthimios M C Skoulakis

doi:10.1371/journal.pone.0152345

Abstract

The biophysical mechanism of the sense of smell, or olfaction, is still highly debated. The mainstream explanation argues for a shape-based recognition of odorant molecules by olfactory receptors, while recent investigations suggest the primary olfactory event to be triggered by a vibrationally-assisted electron transfer reaction. We consider this controversy by studying the influence of a receptor on the vibrational properties of an odorant in atomistic details as the coupling between electronic degrees of freedom of the receptor and the vibrations of the odorant is the key parameter of the vibrationally-assisted electron transfer. Through molecular dynamics simulations we elucidate the binding specificity of a receptor towards acetophenone odorant. The vibrational properties of acetophenone inside the receptor are then studied by the polarizable embedding density functional theory approach, allowing to quantify protein-odorant interactions. Finally, we judge whether the effects of the protein provide any indications towards the existing theories of olfaction.

Highlights

Through the five basic senses—hearing, taste, vision, touch and smell—animals and human beings are able to perceive their environment
We present and discuss the results of the molecular dynamics (MD) simulations of acetophenone and pentanol inside the model olfactory receptors (ORs) and demonstrate long time binding for acetophenone by analysing the time dependencies of bond lengths, root-mean-square displacement (RMSD) and binding energies between the odorants and the rest of the system
Three amino acids surrounding the binding site were chosen for each odorant and the distances between those were calculated over the entire simulation

Summary

Introduction

Through the five basic senses—hearing, taste, vision, touch and smell—animals and human beings are able to perceive their environment. The fundamental mechanism of smell, or olfaction, is still somewhat unclear. It is highly debated how different olfactory receptors (ORs) detect odorants [3,4,5,6,7,8,9] and two different explanations have evolved at present. One argues for a so-called lock-and-key mechanism [9,10,11,12], where the olfactory receptor is forced to change its conformation upon odorant binding thereby leading to signalling. The lock-and-key mechanism relies on the recognition of size and shape of an odorant as the sole factors to distinguish between different odorant molecules. As deuteration does not change the shape of a molecule the PLOS ONE | DOI:10.1371/journal.pone.0152345. As deuteration does not change the shape of a molecule the PLOS ONE | DOI:10.1371/journal.pone.0152345 March 25, 2016

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