Olfactory Receptor Proteins - Bioelectronic Nose: Integration of Biotechnology and Nanotechnology - page 57

Fig. 3.4 a Schematic representation of the GPCR free energy hypersurface (see text). b Different
stabilization of the GPCR 3D structure by agonists for the β2 adrenergic receptor and the rhodop-
sin receptor. This figure has been reprinted from [ 37 ], with permission

3.4 Olfactory Receptors Molecular Modeling and

Virtual Screening

According to Kontoyianni and Liu, only 46 of the about 800 GPCRs found in the
human genome have been assayed with small molecules [ 41 ]. Indeed, a vast major-
ity of GPCRs has not been experimentally characterized, in particular ORs whose
genes have been, mostly, discovered in silico by analyses of sequenced genomes
[ 42 ], although Buck and Axel [ 7 ] had previously uncovered the existence of a novel
multigene family encoding odorant receptors. Most ORs are thus orphan, meaning
that their ligands remain unknown. Therefore, one way of obtaining clues about
these odorant ligands is to use the knowledge acquired from 3D GPCRs structure
solved employing rational computer-aided techniques such as molecular modeling
and virtual screening [ 43 ]. Molecular modeling is based on the properties of ho-
mologous proteins; hence this technique is also known as “homology modeling”.
Two proteins are homologous if they descend from a common ancestor and, as
such, they often have conserved similar sequences, 3D structures and functions.