Mechanism for Olfactory Receptor-Odorant Interactions

Peter C. Lai, Michael S. Singer, Gordon M. Shepherd, Chiquito J. Crasto

Abstract

Olfactory Receptors (OR) constitutes the human genome's largest gene family. Homology and ab initio modeling techniques have been employed to structurally characterize ORs. We have extended the results of a previous modeling study to understand long term interactions between the OR and ligand. Our results for in vacuo, molecular dynamics simulations of the rat I7 OR model and ten aldehyde ligands indicate that the ligand attempts to periodically exit the binding region of the OR and then reenter it. It also appears that this behavior is periodic as evidenced by dynamical structural changes in the binding pocket as the simulation proceeded. The exit events were strongly correlated with significant structural changes. Our results indicate that the exit-reentry events might be related to the binding strengths of the ligands with the OR from a previous experimental study.

Results

For each simulation run the results show figures of the energy minimized docked position of the ligand, the maximum exit from Lys164 in the binding pocket, a graph of the dynamic characteristics of the ligand and key amino acid residues within the binding pocket and a movie that shows the exit event. Complete movies of the simulation are available by email request from Chiquito Crasto
Ligand Name PDB formatted file of minimized position of ligand in OR binding pocket Figure of Minimized Docking Position for the ligand Figure of "exit" position of the ligand Graph showing the characteristics of distance and angle behavior of ligand and amino acids in the binding pocket Movie of exit event
n-octanal Minimized docked positional parameters Energy Minimized Position Exit Position Binding Pocket Characteristics Exit Event Movie
trans-2-octenal Minimized docked positional parameters Energy Minimized Position Exit Position Binding Pocket Characteristics Exit Event Movie
2-octynal Minimized docked positional parameters Energy Minimized Position Exit Position Binding Pocket Characteristics Exit Event Movie
trans-trans-2,4-octadienal Minimized docked positional parameters Energy Minimized Position Exit Position Binding Pocket Characteristics Exit Event Movie
tetrahydrocitral (3,7-dimethyloctanal) Minimized docked positional parameters Energy Minimized Position Exit Position Binding Pocket Characteristics Exit Event Movie
7-methyloctanal Minimized docked positional parameters Energy Minimized Position Exit Position Binding Pocket Characteristics Exit Event Movie
3-methyl-4-(4-methyl-cyclohexyl)-propanal Minimized docked positional parameters Energy Minimized Position Exit Position Binding Pocket Characteristics Exit Event Movie
citronellal (3,7-dimethyl-6-octenal) Minimized docked positional parameters Energy Minimized Position Exit Position Binding Pocket Characteristics Exit Event Movie
citral (3,7-dimethyl-2,6-octadienal) Minimized docked positional parameters Energy Minimized Position Exit Position Binding Pocket Characteristics Exit Event Movie
2,5,7-trimethyl-2,6-octadienal Minimized docked positional parameters Energy Minimized Position Exit Position Binding Pocket Characteristics Exit Event Movie