A Hit Map-Based Statistical Method to Predict Best Ligands for Orphan Olfactory Receptors: Natural Key Odorants Versus Lock Picks

Smell is a multidimensional chemical sense. It creates a perception of our odorous environment by integrating the information of a plethora of volatile chemicals with other sensory inputs, emotions and memories. We are almost always exposed to odorant mixtures, not just single chemicals. Olfactory processing of complex odorant mixtures, such as coffee or wine, first is decoded at the site of perception by the hundreds of different olfactory receptor types, each residing in the cilia of their olfactory sensory neurons in the nose. Often, only a few odorants from many are essential to determine complex olfactory perception. But merely using the chemical structure of odorants is insufficient to identify and predict characteristic odor qualities and low odor thresholds. An understanding of odorant coding critically depends on knowledge about the interaction of key odorants of biologically relevant odor bouquets with their best cognate receptors. Here, we describe a hit map-based method of correlating the information content of all bioassay-tested odorants with their cognate odorant-receptor frequency in four phylogenetic subsets of human olfactory/chemosensory receptors.