Chemical Senses Vol. 29 No. 7 © Oxford University Press
2004; all rights reserved
Predicted 3-D Structures for Mouse I7 and Rat I7 Olfactory Receptors and Comparison of Predicted Odor Recognition Profiles with Experiment
Materials and Process Simulation Center (MC: 139–74), California Institute of Technology, Pasadena, CA 91125, USA
Correspondence to be sent to: William A. Goddard, Materials and Process Simulation Center (MC: 139–74), California Institute of Technology, Pasadena, CA 91125, USA. e-mail: wag{at}wag.caltech.edu
The first step in the perception of an odor is the activation of one or more olfactory receptors (ORs) following binding of the odorant molecule to the OR. In order to initiate the process of determining how the molecular level receptor-odorant interactions are related to odor perception, we used the MembStruk computational method to predict the three-dimensional (3-D) structure of the I7 OR for both mouse and rat. We then used the HierDock ligand docking computational method to predict the binding site and binding energy for the library of 56 odorants to these receptors for which experiment response data are now available. We find that the predicted 3-D structures of the mouse and rat I7 OR lead to predictions of odorant binding that are in good agreement with the experimental results, thus validating the accuracy of both the 3-D structure and the predicted binding site. In particular we predict that heptanal and octanal both bind strongly to both mouse and rat I7 ORs, which conflicts with the older literature but agrees with recent experiments. To provide the basis of additional validations of our 3-D structures, we also report the odorant binding site for a new odorant (8-hydroxy-octanal) with a novel functionality designed to bind strongly to mouse I7. Such validated computational methods should be very useful in predicting the structure and function of many other ORs.
Key words: G protein coupled receptor, hydrogen bonds, molecular dynamics, transmembrane domain
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