Molecular Modeling of Olfactory Receptors


Wely B. Floriano1, Nagarajan Vaidehi1, Michael S. Singer2, Gordon M. Shepherd2, Linda B. Buck3, Betina Malnic3, and William A. Goddard III1


1Materials Simulation Center, California Institute of Technology, mail code BI 139-74, Pasadena, CA 91125.

2Section of Neurobiology, Yale University School of Medicine, 236 FMB, 333 Cedar Street, New Haven, CT 06510.

3Howard Hughes Medical Institute and Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, Massachusetts 02115.



Olfactory Receptors (ORs) are transmembrane proteins that belong to the G protein-coupled receptor family (GPCR). They are believed to initiate the transduction process involved in the recognition of odorants. Their tridimensional (3D) structure has not been determined experimentally, but ORs are predicted to have seven helical transmembrane domains connected by loops, similarly to other GPCRs. Understanding the odor recognition process at a molecular level has practical implications for the fragrance industry and defense applications. Our goal is to model the 3D structure of olfactory receptors, perform docking of odor ligands (from an odor library that is being compiled) to the models and investigate the odor recognition process at a molecular level. The expected outcome is a general methodology for modeling transmembrane proteins, and a knowledge of the odor recognition process that may lead us to our ultimate goal: the molecular design of olfactory receptors for specific odor ligands. We will present our proposed strategy for this problem and our latest results.



This work is part of a Department of Defense Multidiciplinary University Research Initiative (ONR/MURI) project involving Caltech, the Howard Hughes Medical Institute, Harvard Medical School, and Yale University. Support for the Materials Simulation Center (MSC) facilities come from the Department of Energy, Seiko-Epson, BP Chemical, Exxon, National Science Foundation, Saudi Aramco, Chevron Corp., Owens-Corning, NASA, Asahi Chemical, Beckman Institute, Office of Naval Research, Army Research Office, and Avery-Dennison Corp. Some of the calculations are carried out at the Illinois National Center for Supercomputing Applications (NCSA), funded by the National Science Foundation (NSF).


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