Developing human olfactory network and exploring olfactory receptor-odorant interaction

The Olfactory receptor (OR)-odorant interactions are perplexed. ORs can bind to structurally diverse odorants associated with one or more odor percepts. Various attempts have been made to understand the intricacies of OR-odorant interaction. In this study, experimentally documented OR-odorant interactions are investigated comprehensively to; (a) suggest potential odor percepts for ORs based on the OR-OR network; (b) determine how odorants interacting with specific ORs differ in terms of inherent pharmacophoric features and molecular properties, (c) identify molecular interactions that explained OR-odorant interactions of selective ORs; and (d) predict the probable role of ORs other than olfaction. Human olfactory receptor network (hORnet) is developed to study possible odor percepts for ORs. We identified six molecular properties which showed variation and significant patterns to differentiate odorants binding with five ORs. The pharmacophore analysis revealed that odorants subset of five ORs follow similar pharmacophore hypothesis, (one hydrogen acceptor and two hydrophobic regions) but differ in terms of distance and orientation of pharmacophoric features. To ascertain the binding site residues and key interactions between the selected ORs and their interacting odorants, 3D-structure modelling, docking and molecular dynamics studies were carried out. Lastly, the potential role of ORs beyond olfaction is explored. A human OR-OR network was developed to suggest possible odor percepts for ORs using empirically proven OR-odorant interactions. We sought to find out significant characteristics, molecular properties, and molecular interactions that could explain OR-odorant interactions and add to the understanding of the complex issue of odor perception.Communicated by Ramaswamy H. Sarma.