Staff member

Olfactory receptors (ORs) are transmembrane proteins that interact with odorant molecules, triggering the first step in the mechanism of olfaction. They also occupy a large part of mammalian genome and their dysfunction is involved in some degenerative diseases. Proteins structure is related to their function, but experimentally determining the three-dimensional structure of ORs is tricky. However, recent advances in bioinformatics have made it easier. The objectives of this project were to computationally model several ORs and to study their interactions with odorants. We carried out a comparative modelling process, using Chimera and Modeller programs as alignment, visualization and 3D reconstruction tools. After validating the models by several procedures, we performed docking experiments with DOCK. We predicted binding pockets location and studied which odorants bind which ORs, comparing our results with electrophysiological measures of olfactory neurons activity. At the end, we successfully built six mouse ORs models and tested them against 24 common odorants, obtaining a good correlation with previous studies and thus validating our protocol. Moreover, we reconstructed eight human ORs which had never been modelled before, though their predicted interactions with 63 odorants were not clearly correlated to previous experimental studies. In this way, we have shown the efficiency of these computational algorithms, which can contribute to the research about biological processes such as the mechanism of olfaction. With small improvements, they could be in an early future a suitable alternative to experimental approaches, leading to accurate protein models in a practical, faster and easier way.

JTD