Novel Paradigm for Odorant-Olfactory Receptor Interactions

This opinion paper recommends a novel methodology to mechanistically elucidate the interactions between olfactory receptors and odorant molecules. Preliminary results presented here show diffusion of odorant-ligand molecules from outside the olfactory receptor protein into the receptor binding region. This notion marks a sharp contrast with earlier computational studies related to olfactory receptor-odorant interactions. These have drawn conclusions from static or dynamic studies that have started from the ligand already docked in a preferred configuration in the receptor’s binding region. Dynamic simulations studies that begin by tracking the approach of the odorant from outside the protein, its transit to the receptor binding region, followed by tracking the rest of the receptor-odorant interactions will allow the determination of protein structural changes: 1) that facilitate the odorant path; 2) that facilitate specific interactions between amino acids and the odorant; 3) that ide