R. J. Stevenson, An initial evaluation of the functions of human olfaction, Chem. Senses, vol.35, pp.3-20, 2010.

C. S. Sell, On the unpredictability of odor, Angew. Chem. Int. Ed, vol.45, pp.6254-6261, 2006.

A. Keller, R. C. Gerkin, Y. Guan, A. Dhurandhar, G. Turu et al., Predicting human olfactory perception from chemical features of odor molecules, Science, vol.355, pp.820-826, 2017.
DOI : 10.1126/science.aal2014

URL : https://science.sciencemag.org/content/sci/355/6327/820.full.pdf

S. Firestein, How the olfactory system makes sense of scents, Nature, vol.413, pp.211-218, 2001.

B. Malnic, J. Hirono, T. Sato, and L. B. Buck, Combinatorial receptor codes for odors, Cell, vol.96, pp.713-723, 1999.

C. Bushdid, M. O. Magnasco, L. B. Vosshall, and A. Keller, Humans can discriminate more than 1 trillion olfactory stimuli, Science, vol.343, pp.1370-1372, 2014.

C. W. Yu, K. A. Prokop-prigge, L. A. Warrenburg, and J. D. Mainland, Drawing the Borders of Olfactory Space, Chem. Senses, vol.40, pp.565-565, 2015.

R. J. Stevenson, An initial evaluation of the functions of human olfaction, Chem. Senses, vol.35, pp.3-20, 2010.

C. S. Sell, On the unpredictability of odor, Angew. Chem. Int. Ed, vol.45, pp.6254-6261, 2006.

A. Keller, R. C. Gerkin, Y. Guan, A. Dhurandhar, G. Turu et al., Predicting human olfactory perception from chemical features of odor molecules, Science, vol.355, pp.820-826, 2017.

S. Firestein, How the olfactory system makes sense of scents, Nature, vol.413, pp.211-218, 2001.

B. Malnic, J. Hirono, T. Sato, and L. B. Buck, Combinatorial receptor codes for odors, Cell, vol.96, pp.713-723, 1999.

C. Bushdid, M. O. Magnasco, L. B. Vosshall, and A. Keller, Humans can discriminate more than 1 trillion olfactory stimuli, Science, vol.343, pp.1370-1372, 2014.

C. W. Yu, K. A. Prokop-prigge, L. A. Warrenburg, and J. D. Mainland, Drawing the Borders of Olfactory Space, Chem. Senses, vol.40, pp.565-565, 2015.

J. P. Brun and X. Fernandez, Parfums antiques-De l'Archéologue au Chimiste, 2015.

C. Classen, D. Howes, and A. Synnott, Aroma-The Cultural History of Smell, 1994.

A. L. Guérer, Odorat et Goût-De la neurobiologie des sens chimique aux applications, pp.11-14, 2012.

A. Keller and D. Malaspina, Hidden consequences of olfactory dysfunction: a patient report series, BMC Ear Nose Throat Disord, vol.13, issue.1, p.8, 2013.

I. Croy, S. Nordin, and T. Hummel, Olfactory Disorders and Quality of Life-An Updated Review, Chem. Senses, vol.39, pp.185-194, 2014.

R. J. Stevenson, An initial evaluation of the functions of human olfaction, Chem. Senses, vol.35, pp.3-20, 2010.

S. Richardson, What is Postgenomics? In: 4S Annual Meeting Crowne Plaza Cleveland City Center Hotel, pp.25-36

U. J. Meierhenrich, J. Golebiowski, X. Fernandez, and D. Cabrol-bass,

, Les bases moléculaires des premières étapes de l'olfaction. L'Actualité Chimique, vol.289, pp.29-40, 2005.

C. Sezille, A. Fournel, C. Rouby, F. Rinck, and M. Bensafi, Hedonic appreciation and verbal description of pleasant and unpleasant odors in untrained, trainee cooks, flavorists and perfumers, Front. Psychol, vol.5, p.12, 2014.
URL : https://hal.archives-ouvertes.fr/halshs-00997899

C. Bushdid, M. O. Magnasco, L. B. Vosshall, and A. Keller, Humans can discriminate more than 1 trillion olfactory stimuli, Science, vol.343, pp.1370-1372, 2014.
DOI : 10.1126/science.1249168

URL : http://europepmc.org/articles/pmc4483192?pdf=render

T. Weiss, K. Snitz, A. Yablonka, R. M. Khan, D. Gafsou et al., Perceptual convergence of multi-component mixtures in olfaction implies an olfactory white, Proc. Natl. Acad. Sci. U. S. A, vol.109, 2012.

S. Nicklaus and S. Issanchou, Gustation, olfaction et préférences alimentaires chez l'enfant

R. Salesse and E. Gervais, Odorat et Goût-De la neurobiologie des sens chimique aux applications, pp.359-371, 2012.

B. Schaal, L. Marlier, and R. Soussignan, Human foetuses learn odours from their pregnant mother's diet, Chem. Senses, vol.25, pp.729-737, 2000.
DOI : 10.1093/chemse/25.6.729

URL : https://academic.oup.com/chemse/article-pdf/25/6/729/9752909/250729.pdf

F. Kermen, A. Chakirian, C. Sezille, P. Joussain, G. L. Goff et al.,

A. Mandairon, C. Didier, M. Rouby, and . Bensafi, Molecular complexity determines the number of olfactory notes and the pleasantness of smells, Sci. Rep, vol.1, p.206, 2011.

A. Keller, R. C. Gerkin, Y. Guan, A. Dhurandhar, G. Turu et al., Predicting human olfactory perception from chemical features of odor molecules, Science, vol.355, pp.820-826, 2017.

E. A. Krusemark, L. R. Novak, D. R. Gitelman, and W. Li, When the sense of smell meets emotion: anxiety-state-dependent olfactory processing and neural circuitry adaptation, J. Neurosci, vol.33, pp.15324-15332, 2013.

Y. Sugawara, A. Shigetho, M. Yoneda, T. Tuchiya, T. Matumura et al., Relationship between mood change, odour and its physiological effects in humans while inhaling the fragrances of essential oils as well as linalool and its enantiomers, Molecules, vol.18, pp.3312-3338, 2013.

Y. Nikaido, S. Miyata, and T. Nakashima, Mixture of cis-3-hexenol and trans-2-hexenal attenuates behavioral and stress responses induced by 2,5-dihydro-2,4,5-trimethylthiazoline and electric footshock stress in rats, Physiol. Behav, vol.103, pp.547-556, 2011.

K. D. Perring, . Volatility, and . Substantivity, The Chemistry of FragrancesFrom Perfumer to Consumer, pp.199-213, 2006.

C. S. Sell, The Chemistry of Fragrances-From Perfumer to Consumer, pp.52-131, 2006.

K. J. Rossiter, Structure-Odor Relationships, Chem. Rev, vol.96, pp.3201-3240, 1996.

P. Kraft, J. A. Bajgrowicz, C. Denis, and G. Frater, Odds and trends: Recent developments in the chemistry of odorants, Angew. Chem. Int. Ed, vol.39, pp.2981-3010, 2000.

C. S. Sell, On the unpredictability of odor, Angew. Chem. Int. Ed, vol.45, pp.6254-6261, 2006.

M. Chastrette and D. Zakarya, The Human Sense of Smell, pp.77-95, 1991.

L. Buck and R. Axel, A novel multigene family may encode odorant receptors: a molecular basis for odor recognition, Cell, vol.65, pp.175-187, 1991.

D. Pierron, N. G. Cortes, T. Letellier, and L. I. Grossman, Current relaxation of selection on the human genome: tolerance of deleterious mutations on olfactory receptors, Mol. Phylogenet. Evol, vol.66, pp.558-564, 2013.

S. Robin, P. Quignon, and F. Galibert, Odorat et Goût-De la neurobiologie des sens chimiques aux applications, Génétique et évolution des récepteurs olfactifs chez les Vertébrés, pp.291-309, 2012.

B. Malnic, J. Hirono, T. Sato, and L. B. Buck, Combinatorial receptor codes for odors, Cell, vol.96, pp.713-723, 1999.

B. Schilling, R. Kaiser, A. Natsch, and M. Gautschi, Investigation of odors in the fragrance industry, Chemoecology, vol.20, pp.135-147, 2010.

L. Turin, A spectroscopic mechanism for primary olfactory reception, Chem. Senses, vol.21, pp.773-791, 1996.

E. Block, S. Jang, H. Matsunami, S. Sekharan, B. Dethier et al.,

Z. Li, S. N. Li, M. Lodge, H. Ozbil, S. F. Jiang et al., Implausibility of the vibrational theory of olfaction, Proc. Natl. Acad. Sci. U. S. A, vol.112, pp.2766-2774, 2015.

L. B. Vosshall, Laying a controversial smell theory to rest, Proc. Natl. Acad. Sci. U. S. A, vol.112, pp.6525-6526, 2015.

C. A. De-march, Y. Yu, M. J. Ni, K. A. Adipietro, H. Matsunami et al., Conserved Residues Control Activation of Mammalian G Protein-Coupled Odorant Receptors, J. Am. Chem. Soc, vol.137, pp.8611-8616, 2015.

Y. Yu, C. A. De-march, M. J. Ni, K. A. Adipietro, J. Golebiowski et al., Responsiveness of G protein-coupled odorant receptors is partially attributed to the activation mechanism, Proc. Natl. Acad. Sci. U. S. A, vol.112, pp.14966-14971, 2015.

C. A. De-march and J. Golebiowski, A computational microscope focused on the sense of smell, Biochimie, vol.107, pp.3-10, 2014.

J. Topin, C. A. De-march, L. Charlier, C. Ronin, S. Antonczak et al., Discrimination between olfactory receptor agonists and non-agonists, Chemistry, vol.20, pp.10227-10230, 2014.

C. A. De-march, S. Ryu, G. Sicard, C. Moon, and J. Golebiowski, Structure-odour relationships reviewed in the postgenomic era. Flavour Fragr, J, vol.30, pp.342-361, 2015.

J. F. Mcrae, J. D. Mainland, S. R. Jaeger, K. A. Adipietro, H. Matsunami et al., Genetic variation in the odorant receptor OR2J3 is associated with the ability to detect the "grassy" smelling odor, cis-3-hexen-1-ol, Chem. Senses, vol.37, pp.585-593, 2012.

A. J. Chang, F. E. Ortega, J. Riegler, D. V. Madison, and M. A. Krasnow, Oxygen regulation of breathing through an olfactory receptor activated by lactate, Nature, vol.527, pp.240-244, 2015.

J. L. Pluznick, R. J. Protzko, H. Gevorgyan, Z. Peterlin, A. Sipos et al.,

F. Wan, T. Rey, S. J. Wang, M. Firestein, J. I. Yanagisawa et al.,

J. Caplan, Olfactory receptor responding to gut microbiota-derived signals plays a role in renin secretion and blood pressure regulation, Proc. Natl. Acad. Sci. U. S. A, vol.110, pp.4410-4415, 2013.

G. Sanz, I. Leray, A. Dewaele, J. Sobilo, S. Lerondel et al.,

L. M. Pajot-augy and . Mir, Promotion of cancer cell invasiveness and metastasis emergence caused by olfactory receptor stimulation, PLoS One, vol.9, p.85110, 2014.

C. W. Yu, K. A. Prokop-prigge, L. A. Warrenburg, and J. D. Mainland, Drawing the Borders of Olfactory Space, Chem. Senses, vol.40, pp.565-565, 2015.

G. Sanz, T. Thomas-danguin, H. Hamdani-el, C. Le-poupon, L. Briand et al.,

A. Guichard and . Tromelin, Relationships between molecular structure and perceived odor quality of ligands for a human olfactory receptor, Chem. Senses, vol.33, pp.639-653, 2008.

G. Sanz, C. Schlegel, J. C. Pernollet, and L. Briand, Comparison of odorant specificity of two human olfactory receptors from different phylogenetic classes and evidence for antagonism, Chem. Senses, vol.30, pp.69-80, 2005.

S. Bavan, B. Sherman, C. W. Luetje, and T. Abaffy, Discovery of novel ligands for mouse olfactory receptor MOR42-3 using an in silico screening approach and in vitro validation, PloS One, vol.9, p.92064, 2014.

T. Abaffy, J. R. Bain, M. J. Muehlbauer, I. Spasojevic, S. Lodha et al., A Testosterone Metabolite 19-Hydroxyandrostenedione Induces Neuroendocrine Trans-Differentiation of Prostate Cancer Cells via an Ectopic Olfactory Receptor, Front. Ocol, vol.8, p.162, 2018.

S. M. Boyle, S. Mcinally, and A. Ray, Expanding the olfactory code by in silico decoding of odorreceptor chemical space, vol.2, p.1120, 2013.

M. Schmuker, M. De-bruyne, M. Hahnel, and G. Schneider, Predicting olfactory receptor neuron responses from odorant structure, Chem. Cent. J, vol.4, pp.1-11, 2007.

K. Schwab, The Fourth Industrial Revolution, World Economic Forum, 2016.

, Dragon Software for Molecular Descriptor Calculation, 2014.

B. Malnic, J. Hirono, T. Sato, and L. B. Buck, Combinatorial receptor codes for odors, Cell, vol.96, pp.713-723, 1999.

H. Saito, Q. Chi, H. Zhuang, H. Matsunami, and J. D. Mainland, Odor coding by a Mammalian receptor repertoire, Sci. Signal, vol.2, p.9, 2009.

C. Geithe, G. Andersen, A. Malki, and D. Krautwurst, A Butter Aroma Recombinate Activates Human Class-I Odorant Receptors, J. Agric. Food Chem, vol.63, pp.9410-9420, 2015.

J. D. Mainland, A. Keller, Y. R. Li, T. Zhou, C. Trimmer et al.,

W. L. Adipietro, H. Liu, S. Zhuang, S. S. Zhan, A. Lee et al., The missense of smell: functional variability in the human odorant receptor repertoire, Nat. Neurosci, vol.17, pp.114-120, 2014.

K. A. Adipietro, J. D. Mainland, and H. Matsunami, Functional evolution of mammalian odorant receptors, PLoS Genet, vol.8, p.1002821, 2012.

C. A. De-march, Y. Yu, M. J. Ni, K. A. Adipietro, H. Matsunami et al., Conserved Residues Control Activation of Mammalian G Protein-Coupled Odorant Receptors, J. Am. Chem. Soc, vol.137, pp.8611-8616, 2015.

Y. Yu, C. A. De-march, M. J. Ni, K. A. Adipietro, J. Golebiowski et al., Responsiveness of G protein-coupled odorant receptors is partially attributed to the activation mechanism, Proc. Natl. Acad. Sci. U. S. A, vol.112, pp.14966-14971, 2015.

C. Bushdid, C. A. De-march, S. Fiorucci, H. Matsunami, and J. Golebiowski, Agonists of GProtein-Coupled Odorant Receptors Are Predicted from Chemical Features, TALETE srl. Dragon Software for Molecular Descriptor Calculation, vol.9, p.9, 2014.

M. R. Berthold, N. Cebron, F. Dill, T. R. Gabriel, T. Kotter et al.,

B. Thiel and . Wiswedel, KNIME: The Konstanz Information Miner, Data Analysis, Machine Learning and Applications. Studies in Classification, Data Analysis, and Knowledge Organization, 2008.

N. Eswar, B. Webb, M. A. Marti-renom, M. S. Madhusudhan, D. Eramian et al.,

A. Pieper and . Sali, Comparative protein structure modeling using Modeller, Curr. Protoc. Bioinformatics Chapter, pp.5-6, 2006.

L. Charlier, J. Topin, C. A. De-march, P. C. Lai, C. J. Crasto et al., Molecular Modelling of Odorant/Olfactory Receptor Complexes, Methods Mol. Biol, vol.1003, pp.53-65, 2013.

C. A. De-march, S. K. Kim, S. Antonczak, W. A. Goddard, and J. Golebiowski, G proteincoupled odorant receptors: from sequence to structure, Protein Sci, vol.24, pp.1543-1548, 2015.

V. Cvicek, W. A. Goddard, and R. Abrol, Structure-Based Sequence Alignment of the Transmembrane Domains of All Human GPCRs: Phylogenetic, Structural and Functional Implications, PLoS Comput. Biol, vol.12, p.1004805, 2016.

D. Krautwurst, K. W. Yau, and R. R. Reed, Identification of ligands for olfactory receptors by functional expression of a receptor library, Cell, vol.95, pp.917-926, 1998.

Y. R. Li and H. Matsunami, Activation state of the M3 muscarinic acetylcholine receptor modulates mammalian odorant receptor signaling, Sci. Signal, vol.4, p.1, 2011.

B. F. Binkowski, F. Fan, and K. V. Wood, Luminescent biosensors for real-time monitoring of intracellular cAMP, Methods Mol. Biol, vol.756, pp.263-271, 2011.

H. Zhuang and H. Matsunami, Evaluating cell-surface expression and measuring activation of mammalian odorant receptors in heterologous cells, Nat. Protoc, vol.3, pp.1402-1413, 2008.

H. Zhuang and H. Matsunami, Synergism of accessory factors in functional expression of mammalian odorant receptors, J. Biol. Chem, vol.282, pp.15284-15293, 2007.

R. C. Araneda, A. D. Kini, and S. Firestein, The molecular receptive range of an odorant receptor, Nat. Neurosci, vol.3, pp.1248-1255, 2000.

E. Poivet, Z. Peterlin, N. Tahirova, L. Xu, C. Altomare et al., Applying medicinal chemistry strategies to understand odorant discrimination, Nat. Commun, vol.7, p.11157, 2016.
DOI : 10.1038/ncomms11157

URL : https://www.nature.com/articles/ncomms11157.pdf

E. Poivet, N. Tahirova, Z. Peterlin, L. Xu, D. J. Zou et al., Functional odor classification through a medicinal chemistry approach, Sci. Adv, vol.4, p.6086, 2018.
DOI : 10.1126/sciadv.aao6086

URL : https://doi.org/10.1126/sciadv.aao6086

Z. Peterlin, Y. Li, G. Sun, R. Shah, S. Firestein et al., The importance of odorant conformation to the binding and activation of a representative olfactory receptor, Chemistry & biology, vol.15, pp.1317-1327, 2008.

H. Zhuang and H. Matsunami, Evaluating cell-surface expression and measuring activation of mammalian odorant receptors in heterologous cells, Nat. Protoc, vol.3, pp.1402-1413, 2008.

H. Saito, Q. Chi, H. Zhuang, H. Matsunami, and J. D. Mainland, Odor coding by a Mammalian receptor repertoire, Sci. Signal, vol.2, p.9, 2009.
DOI : 10.1016/j.neures.2009.09.277

K. A. Adipietro, J. D. Mainland, and H. Matsunami, Functional evolution of mammalian odorant receptors, PLoS Genet, vol.8, p.1002821, 2012.
DOI : 10.1371/journal.pgen.1002821

URL : https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1002821&type=printable

J. D. Mainland, A. Keller, Y. R. Li, T. Zhou, C. Trimmer et al.,

W. L. Adipietro, H. Liu, S. Zhuang, S. S. Zhan, A. Lee et al., The missense of smell: functional variability in the human odorant receptor repertoire, Nat. Neurosci, vol.17, pp.114-120, 2014.

G. Sanz, C. Schlegel, J. C. Pernollet, and L. Briand, Comparison of odorant specificity of two human olfactory receptors from different phylogenetic classes and evidence for antagonism, Chem. Senses, vol.30, pp.69-80, 2005.

S. Li, L. Ahmed, R. Zhang, Y. Pan, H. Matsunami et al., Smelling Sulfur: Copper and Silver Regulate the Response of Human Odorant Receptor OR2T11 to Low-Molecular-Weight Thiols, J. Am. Chem. Soc, vol.138, pp.13281-13288, 2016.

C. Geithe, F. Noe, J. Kreissl, and D. Krautwurst, The Broadly Tuned Odorant Receptor OR1A1 is Highly Selective for 3-Methyl-2,4-nonanedione, a Key Food Odorant in Aged Wines, Tea, and Other Foods, Chem. Senses, vol.42, pp.181-193, 2017.

F. Noe, J. Polster, C. Geithe, M. Kotthoff, P. Schieberle et al., OR2M3: A Highly Specific and Narrowly Tuned Human Odorant Receptor for the Sensitive Detection of Onion Key Food Odorant 3-Mercapto-2-methylpentan-1-ol, Chem. Senses, vol.42, pp.195-210, 2017.

L. Ahmed, Y. Zhang, E. Block, M. Buehl, M. J. Corr et al., Molecular mechanism of activation of human musk receptors OR5AN1 and OR1A1 by (R)-muscone and diverse other musk-smelling compounds, Proc. Natl. Acad. Sci. U. S. A, vol.115, pp.3950-3958, 2018.

Y. Niimura, Olfactory receptor multigene family in vertebrates: from the viewpoint of evolutionary genomics, Curr. Genomics, vol.13, pp.103-114, 2012.

C. Bushdid, M. O. Magnasco, L. B. Vosshall, and A. Keller, Humans can discriminate more than 1 trillion olfactory stimuli, Science, vol.343, pp.1370-1372, 2014.

N. Kang and J. Koo, Olfactory receptors in non-chemosensory tissues, BMB Rep, vol.45, pp.612-622, 2012.

B. Malnic, J. Hirono, T. Sato, and L. B. Buck, Combinatorial receptor codes for odors, Cell, vol.96, pp.713-723, 1999.

C. A. De-march, Y. Yu, M. J. Ni, K. A. Adipietro, H. Matsunami et al., Conserved Residues Control Activation of Mammalian G Protein-Coupled Odorant Receptors, J. Am. Chem. Soc, vol.137, pp.8611-8616, 2015.

X. J. Yao, G. Velez-ruiz, M. R. Whorton, S. G. Rasmussen, B. T. Devree et al.,

B. Sunahara and . Kobilka, The effect of ligand efficacy on the formation and stability of a GPCR-G protein complex, Proc. Natl. Acad. Sci. U. S. A, vol.106, pp.9501-9506, 2009.

A. Keller, R. C. Gerkin, Y. Guan, A. Dhurandhar, G. Turu et al., Predicting human olfactory perception from chemical features of odor molecules, Science, vol.355, pp.820-826, 2017.

D. Wacker, R. C. Stevens, and B. L. Roth, How Ligands Illuminate GPCR Molecular Pharmacology. Cell, vol.170, pp.414-427, 2017.

S. M. Boyle, S. Mcinally, and A. Ray, Expanding the olfactory code by in silico decoding of odorreceptor chemical space, vol.2, p.1120, 2013.

K. Mansouri and R. S. Judson, In Silico Study of In Vitro GPCR Assays by QSAR Modeling, Methods Mol. Biol, vol.1425, pp.361-381, 2016.

R. Shemesh, A. Toporik, Z. Levine, I. Hecht, G. Rotman et al.,

M. A. Kliger, A. Soffer, D. Rosenberg, Y. Eshel, and . Cohen, Discovery and validation of novel peptide agonists for G-protein-coupled receptors, J. Biol. Chem, vol.283, pp.34643-34649, 2008.

J. Wu, Q. Zhang, W. Wu, T. Pang, H. Hu et al., Predicting Bioactivities of Ligand Molecules Acting with G Protein-coupled Receptors by Combining Weighted Deep Learning and Random Forest, vol.34, pp.2271-2282, 2018.

M. Schmuker, M. De-bruyne, M. Hahnel, and G. Schneider, Predicting olfactory receptor neuron responses from odorant structure, Chem. Cent. J, vol.1, p.11, 2007.

W. Huang, Q. Shen, X. Su, M. Ji, X. Liu et al., BitterX: a tool for understanding bitter taste in humans, Sci. Rep, vol.6, p.23450, 2016.

C. Bushdid, C. A. De-march, H. Matsunami, and J. Golebiowski, Numerical models and in vitro assays to study Odorant Receptors, Methods Mol. Biol, vol.1820, pp.77-93, 2018.

C. Flegel, S. Manteniotis, S. Osthold, H. Hatt, and G. Gisselmann, Expression profile of ectopic olfactory receptors determined by deep sequencing, PloS One, vol.8, p.55368, 2013.

J. Leja, A. Essaghir, M. Essand, K. Wester, K. Oberg et al.,

J. B. Vasmatzis, V. Demoulin, and . Giandomenico, Novel markers for enterochromaffin cells and gastrointestinal neuroendocrine carcinomas, Mod. Pathol, vol.22, pp.261-272, 2009.

J. Weng, J. Wang, X. Hu, F. Wang, M. Ittmann et al., PSGR2, a novel G-protein coupled receptor, is overexpressed in human prostate cancer, Int. J. Cancer, vol.118, pp.1471-1480, 2006.

J. D. Mainland, A. Keller, Y. R. Li, T. Zhou, C. Trimmer et al.,

W. L. Adipietro, H. Liu, S. Zhuang, S. S. Zhan, A. Lee et al., The missense of smell: functional variability in the human odorant receptor repertoire, Nat. Neurosci, vol.17, pp.114-120, 2014.

H. Saito, Q. Chi, H. Zhuang, H. Matsunami, and J. D. Mainland, Odor coding by a Mammalian receptor repertoire, Sci. Signal, vol.2, p.9, 2009.

K. Audouze, A. Tromelin, A. M. Le-bon, C. Belloir, R. K. Petersen et al.,

O. Brunak and . Taboureau, Identification of odorant-receptor interactions by global mapping of the human odorome, PloS One, vol.9, p.93037, 2014.
URL : https://hal.archives-ouvertes.fr/hal-01185026

O. Man, Y. Gilad, and D. , Lancet, Prediction of the odorant binding site of olfactory receptor proteins by human-mouse comparisons, Protein Sci, vol.13, pp.240-254, 2004.

C. A. De-march, S. K. Kim, S. Antonczak, W. A. Goddard, and J. Golebiowski, G proteincoupled odorant receptors: from sequence to structure, Protein Sci, vol.24, pp.1543-1548, 2015.

J. A. Ballesteros and H. Weinstein, Integrated methods for the construction of three-dimensional models and computational probing of structure-function relations in G protein-coupled receptors, Methods Neurosci, vol.25, pp.366-428, 1995.

A. J. Venkatakrishnan, X. Deupi, G. Lebon, C. G. Tate, G. F. Schertler et al., Molecular signatures of G-protein-coupled receptors, Nature, vol.494, pp.185-194, 2013.

J. H. Park, T. Morizumi, Y. Li, J. E. Hong, E. F. Pai et al., Opsin, a Structural Model for Olfactory Receptors?, Angew. Chem. Int. Ed, vol.52, pp.11021-11024, 2013.

C. De-march, J. Topin, E. Bruguera, G. Novikov, K. Ikegami et al., Odorant Receptor 7D4 Activation Dynamics, Angew. Chem. Int. Ed, vol.57, pp.4554-4558, 2018.

H. Zhuang and H. Matsunami, Evaluating cell-surface expression and measuring activation of mammalian odorant receptors in heterologous cells, Nat. Protoc, vol.3, pp.1402-1413, 2008.

A. Keller, H. Zhuang, Q. Chi, L. B. Vosshall, and H. Matsunami, Genetic variation in a human odorant receptor alters odour perception, Nature, vol.449, pp.468-472, 2007.

Y. R. Li and H. Matsunami, Activation state of the M3 muscarinic acetylcholine receptor modulates mammalian odorant receptor signaling, Sci. Signal, vol.4, p.1, 2011.

J. D. Mainland, A. Keller, Y. R. Li, T. Zhou, C. Trimmer et al.,

W. L. Adipietro, H. Liu, S. Zhuang, S. S. Zhan, A. Lee et al., The missense of smell: functional variability in the human odorant receptor repertoire, Nat. Neurosci, vol.17, pp.114-120, 2014.

, Dragon Software for Molecular Descriptor Calculation, 2014.

M. R. Berthold, N. Cebron, F. Dill, T. R. Gabriel, T. Kotter et al.,

B. Thiel and . Wiswedel, KNIME: The Konstanz Information Miner, Data Analysis, Machine Learning and Applications. Studies in Classification, Data Analysis, and Knowledge Organization, 2008.

H. Saito, Q. Chi, H. Zhuang, H. Matsunami, and J. D. Mainland, Odor coding by a Mammalian receptor repertoire, Sci. Signal, vol.2, p.9, 2009.

K. Audouze, A. Tromelin, A. M. Le-bon, C. Belloir, R. K. Petersen et al.,

O. Brunak and . Taboureau, Identification of odorant-receptor interactions by global mapping of the human odorome, PloS One, vol.9, p.93037, 2014.
URL : https://hal.archives-ouvertes.fr/hal-01185026

K. A. Adipietro, J. D. Mainland, and H. Matsunami, Functional evolution of mammalian odorant receptors, PLoS Genet, vol.8, p.1002821, 2012.

Y. Fujita, T. Takahashi, A. Suzuki, K. Kawashima, F. Nara et al., Deorphanization of

, Dresden G protein-coupled receptor for an odorant receptor, J. Recept. Signal Transduct, vol.27, pp.323-334, 2007.

C. Geithe, G. Andersen, A. Malki, and D. Krautwurst, A Butter Aroma Recombinate Activates Human Class-I Odorant Receptors, J. Agric. Food Chem, vol.63, pp.9410-9420, 2015.

N. Jovancevic, A. Dendorfer, M. Matzkies, M. Kovarova, J. C. Heckmann et al.,

L. Boehm, F. Weber, J. Nguemo, J. Semmler, H. Hescheler et al., Medium-chain fatty acids modulate myocardial function via a cardiac odorant receptor, Basic Res. Cardiol, vol.112, p.13, 2017.

A. Veithen, M. Philippeau, and P. Chatelain, High-Throughput Receptor Screening Assay, pp.505-525, 2017.

C. A. De-march, S. K. Kim, S. Antonczak, W. A. Goddard, and J. Golebiowski, G proteincoupled odorant receptors: from sequence to structure, Protein Sci, vol.24, pp.1543-1548, 2015.

N. Eswar, B. Webb, M. A. Marti-renom, M. S. Madhusudhan, D. Eramian et al.,

A. Pieper and . Sali, Comparative protein structure modeling using Modeller, Curr. Protoc. Bioinformatics Chapter, pp.5-6, 2006.

O. Trott and A. J. Olson, AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading, J. Comput. Chem, vol.31, pp.455-461, 2010.

C. Geithe, F. Noe, J. Kreissl, and D. Krautwurst, The Broadly Tuned Odorant Receptor OR1A1 is Highly Selective for 3-Methyl-2,4-nonanedione, a Key Food Odorant in Aged Wines, Tea, and Other Foods, Chem. Senses, vol.42, pp.181-193, 2017.

K. Schmiedeberg, E. Shirokova, H. P. Weber, B. Schilling, W. Meyerhof et al., Structural determinants of odorant recognition by the human olfactory receptors OR1A1 and OR1A2, J. Struct. Biol, vol.159, pp.400-412, 2007.

E. Block, S. Jang, H. Matsunami, S. Sekharan, B. Dethier et al.,

Z. Li, S. N. Li, M. Lodge, H. Ozbil, S. F. Jiang et al., Implausibility of the vibrational theory of olfaction, Proc. Natl. Acad. Sci. U. S. A, vol.112, pp.2766-2774, 2015.

T. Braun, P. Voland, L. Kunz, C. Prinz, and M. Gratzl, Enterochromaffin cells of the human gut: sensors for spices and odorants, Gastroenterology, vol.132, pp.1890-1901, 2007.

Y. Yu, C. A. De-march, M. J. Ni, K. A. Adipietro, J. Golebiowski et al., Responsiveness of G protein-coupled odorant receptors is partially attributed to the activation mechanism, Proc. Natl. Acad. Sci. U. S. A, vol.112, pp.14966-14971, 2015.

K. L. Pierce, R. T. Premont, and R. J. Lefkowitz, Seven-transmembrane receptors, Nat. Rev. Mol. Cell Biol, vol.3, pp.639-650, 2002.

D. M. Rosenbaum, S. G. Rasmussen, and B. K. Kobilka, The structure and function of G-proteincoupled receptors, Nature, vol.459, pp.356-363, 2009.

R. Fredriksson, M. C. Lagerstrom, L. G. Lundin, and H. B. Schioth, The G-protein-coupled receptors in the human genome form five main families. Phylogenetic analysis, paralogon groups, and fingerprints, Mol. Pharmacol, vol.63, pp.1256-1272, 2003.

A. J. Venkatakrishnan, X. Deupi, G. Lebon, C. G. Tate, G. F. Schertler et al., Molecular signatures of G-protein-coupled receptors, Nature, vol.494, pp.185-194, 2013.

K. Palczewski, T. Kumasaka, T. Hori, C. A. Behnke, H. Motoshima et al., Crystal structure of rhodopsin: A G protein-coupled receptor, Science, vol.289, pp.739-745, 2000.

S. G. Rasmussen, B. T. Devree, Y. Zou, A. C. Kruse, K. Y. Chung et al., Crystal structure of the beta2 adrenergic receptor-Gs protein complex, vol.477, pp.549-555, 2011.

Y. Kang, X. E. Zhou, X. Gao, Y. He, W. Liu et al.,

G. W. Yefanov, Q. Han, P. W. Xu, J. De-waal, M. H. Ke et al.,

D. Pascal, N. Van-eps, L. N. Caro, S. A. Vishnivetskiy, R. J. Lee et al.,

S. James, S. Basu, C. E. Roy-chowdhury, J. Conrad, H. Coe et al.,

R. C. Hubbell, V. Stevens, K. Cherezov, H. E. Melcher, and . Xu, Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser, Nature, vol.523, pp.561-567, 2015.

C. A. De-march, S. K. Kim, S. Antonczak, W. A. Goddard, and J. Golebiowski, G proteincoupled odorant receptors: From sequence to structure, Protein Sci, vol.24, pp.1543-1548, 2015.

N. Eswar, B. Webb, M. A. Marti-renom, M. S. Madhusudhan, D. Eramian et al.,

A. Pieper and . Sali, Comparative protein structure modeling using Modeller, Curr. Protoc. Bioinformatics Chapter, pp.5-6, 2006.

C. Zhang, Y. Srinivasan, D. H. Arlow, J. J. Fung, D. Palmer et al.,

R. O. Pandey, D. E. Dror, W. I. Shaw, S. R. Weis, B. K. Coughlin et al., High-resolution crystal structure of human protease-activated receptor 1, Nature, vol.492, pp.387-392, 2012.

C. Bushdid, C. A. De-march, S. Fiorucci, H. Matsunami, and J. Golebiowski, Agonists of GProtein-Coupled Odorant Receptors Are Predicted from Chemical Features, J. Phys. Chem. Lett, vol.9, pp.2235-2240, 2018.

M. Congreve, C. Oswald, and F. H. Marshall, Applying Structure-Based Drug Design Approaches to Allosteric Modulators of GPCRs, Trends Pharmacol. Sci, vol.38, pp.837-847, 2017.

Y. Yu, C. A. De-march, M. J. Ni, K. A. Adipietro, J. Golebiowski et al., Responsiveness of G protein-coupled odorant receptors is partially attributed to the activation mechanism, Proc. Natl. Acad. Sci. U. S. A, vol.112, pp.14966-14971, 2015.

L. Buck and R. Axel, A novel multigene family may encode odorant receptors: a molecular basis for odor recognition, Cell, vol.65, pp.175-187, 1991.

Y. Niimura, Olfactory receptor multigene family in vertebrates: from the viewpoint of evolutionary genomics, Curr. Genomics, vol.13, pp.103-114, 2012.

A. J. Venkatakrishnan, X. Deupi, G. Lebon, C. G. Tate, G. F. Schertler et al., Molecular signatures of G-protein-coupled receptors, Nature, vol.494, pp.185-194, 2013.

C. A. De-march, J. Topin, E. Bruguera, G. Novikov, K. Ikegami et al., Odorant Receptor 7D4 Activation Dynamics, Angew. Chem. Int. Ed, vol.57, pp.4554-4558, 2018.

Y. Yu, C. A. De-march, M. J. Ni, K. A. Adipietro, J. Golebiowski et al., Responsiveness of G protein-coupled odorant receptors is partially attributed to the activation mechanism, Proc. Nat. Acad. Sci. U. S. A, vol.112, pp.14966-14971, 2015.

C. A. De-march, Y. Yu, M. J. Ni, K. A. Adipietro, H. Matsunami et al., Conserved Residues Control Activation of Mammalian G Protein-Coupled Odorant Receptors, J. Am. Chem. Soc, vol.137, pp.8611-8616, 2015.

C. Geithe, J. Protze, F. Kreuchwig, G. Krause, and D. Krautwurst, Structural determinants of a conserved enantiomer-selective carvone binding pocket in the human odorant receptor OR1A1, Cell. Mol. Life Sci, vol.74, pp.4209-4229, 2017.

L. Ahmed, Y. Zhang, E. Block, M. Buehl, M. J. Corr et al., Molecular mechanism of activation of human musk receptors OR5AN1 and OR1A1 by (R)-muscone and diverse other musk-smelling compounds, Proc. Nat. Acad. Sci. U. S. A, vol.115, pp.3950-3958, 2018.

L. Gelis, S. Wolf, H. Hatt, E. M. Neuhaus, and K. Gerwert, Prediction of a ligand-binding niche within a human olfactory receptor by combining site-directed mutagenesis with dynamic homology modeling, Angew. Chem. Int. Ed, vol.51, pp.1274-1278, 2012.

C. A. De-march, S. K. Kim, S. Antonczak, W. A. Goddard, and J. Golebiowski, G proteincoupled odorant receptors: From sequence to structure, Protein Sci, vol.24, pp.1543-1548, 2015.

J. Freitag, J. Krieger, J. Strotmann, and H. Breer, Two classes of olfactory receptors in Xenopus laevis, Neuron, vol.15, pp.1383-1392, 1995.

G. Glusman, A. Bahar, D. Sharon, Y. Pilpel, J. White et al., The olfactory receptor gene superfamily: data mining, classification, and nomenclature, Mamm Genome, vol.11, pp.1016-1023, 2000.

X. Zhang and S. Firestein, The olfactory receptor gene superfamily of the mouse, Nat. Neurosci, vol.5, pp.124-133, 2002.

Y. Niimura and M. Nei, Evolutionary dynamics of olfactory receptor genes in fishes and tetrapods, Proc. Nat. Acad. Sci. U. S. A, vol.102, pp.6039-6044, 2005.

Y. Niimura and M. Nei, Evolution of olfactory receptor genes in the human genome, Proc. Nat. Acad. Sci. U. S. A, vol.100, pp.12235-12240, 2003.

T. Iwata, Y. Niimura, C. Kobayashi, D. Shirakawa, H. Suzuki et al.,

J. Yoshihara and . Hirota, A long-range cis-regulatory element for class I odorant receptor genes, Nature Commun, vol.8, p.885, 2017.

J. Freitag, G. Ludwig, I. Andreini, P. Rossler, and H. Breer, Olfactory receptors in aquatic and terrestrial vertebrates, J. Comp. Physiol. A, vol.183, pp.635-650, 1998.

H. Saito, Q. Chi, H. Zhuang, H. Matsunami, and J. D. Mainland, Odor coding by a Mammalian receptor repertoire, Science signaling, vol.2, p.9, 2009.

D. M. Thal, A. Glukhova, P. M. Sexton, and A. Christopoulos, Structural insights into G-proteincoupled receptor allostery, Nature, vol.559, pp.45-53, 2018.

X. Yuan, S. Raniolo, V. Limongelli, and Y. Xu, The Molecular Mechanism Underlying Ligand Binding to the Membrane-Embedded Site of a G-Protein-Coupled Receptor, J. Chem. Theory Comput, vol.14, pp.2761-2770, 2018.

N. Stanley, L. Pardo, and G. D. Fabritiis, The pathway of ligand entry from the membrane bilayer to a lipid G protein-coupled receptor, Sci. Rep, vol.6, p.22639, 2016.

R. O. Dror, A. C. Pan, D. H. Arlow, D. W. Borhani, P. Maragakis et al.,

. Shaw, Pathway and mechanism of drug binding to G-protein-coupled receptors, Proc. Nat. Acad. Sci. U. S. A, vol.108, pp.13118-13123, 2011.

A. C. Kruse, J. Hu, A. C. Pan, D. H. Arlow, D. M. Rosenbaum et al.,

P. S. Liu, R. O. Chae, D. E. Dror, W. I. Shaw, J. Weis et al., Structure and dynamics of the M3 muscarinic acetylcholine receptor, Nature, vol.482, pp.552-556, 2012.

D. Provasi, A. Bortolato, and M. Filizola, Exploring molecular mechanisms of ligand recognition by opioid receptors with metadynamics, Biochemistry, vol.48, pp.10020-10029, 2009.

M. Sandal, M. Behrens, A. Brockhoff, F. Musiani, A. Giorgetti et al., Evidence for a Transient Additional Ligand Binding Site in the TAS2R46 Bitter Taste Receptor, J. Chem. Theory Comput, vol.11, pp.4439-4449, 2015.

K. Sharma, S. Balfanz, A. Baumann, and S. Korsching, Full rescue of an inactive olfactory receptor mutant by elimination of an allosteric ligand-gating site, Sci. Rep, vol.8, p.9631, 2018.

V. Cvicek, W. A. Goddard, and R. Abrol, Structure-Based Sequence Alignment of the Transmembrane Domains of All Human GPCRs: Phylogenetic, Structural and Functional Implications, PLoS Comput Biol, vol.12, p.1004805, 2016.

J. A. Ballesteros and H. Weinstein, Integrated methods for the construction of three-dimensional models and computational probing of structure-function relations in G protein-coupled receptors, Methods Neurosci, vol.25, pp.366-428, 1995.

C. Bushdid, C. A. De-march, H. Matsunami, and J. Golebiowski, Numerical models and in vitro assays to study Odorant Receptors, Methods Mol. Biol, vol.1820, pp.77-93, 2018.

S. Katada, T. Hirokawa, Y. Oka, M. Suwa, and K. Touhara, Structural basis for a broad but selective ligand spectrum of a mouse olfactory receptor: mapping the odorant-binding site, J. Neurosci, vol.25, pp.1806-1815, 2005.

M. Wheatley, D. Wootten, M. T. Conner, J. Simms, R. Kendrick et al., Lifting the lid on GPCRs: the role of extracellular loops, Br. J. Pharmacol, vol.165, pp.1688-1703, 2012.

K. Audouze, A. Tromelin, A. M. Le-bon, C. Belloir, R. K. Petersen et al.,

O. Brunak and . Taboureau, Identification of odorant-receptor interactions by global mapping of the human odorome, PloS one, vol.9, p.93037, 2014.
URL : https://hal.archives-ouvertes.fr/hal-01185026

L. Charlier, J. Topin, C. Ronin, S. K. Kim, W. A. Goddard et al., How broadly tuned olfactory receptors equally recognize their agonists. Human OR1G1 as a test case, Cell. Mol. Life Sci, vol.69, pp.4205-4213, 2012.

T. Sato, T. Kawasaki, S. Mine, and H. Matsumura,

, Amphipathic Helix 8 of Olfactory Receptors and Other G Protein-Coupled Receptors, Int. J. Mol. Sci, vol.17, p.1930, 2016.

S. Granier and B. Kobilka, A new era of GPCR structural and chemical biology, Nat. Chem. Biol, vol.8, pp.670-673, 2012.
DOI : 10.1038/nchembio.1025

URL : http://europepmc.org/articles/pmc4031315?pdf=render

J. Topin, C. A. De-march, L. Charlier, C. Ronin, S. Antonczak et al., Discrimination between olfactory receptor agonists and non-agonists, Chemistry, vol.20, pp.10227-10230, 2014.
DOI : 10.1002/chem.201402486

A. Dunkel, M. Steinhaus, M. Kotthoff, B. Nowak, D. Krautwurst et al., Nature's chemical signatures in human olfaction: a foodborne perspective for future biotechnology, Angew. Chem. Int. Ed, vol.53, pp.7124-7143, 2014.
DOI : 10.1002/anie.201309508

D. Massberg and H. Hatt, Human Olfactory Receptors: Novel Cellular Functions Outside of the Nose, Physiol. Rev, vol.98, pp.1739-1763, 2018.

A. Malki, J. Fiedler, K. Fricke, I. Ballweg, M. W. Pfaffl et al., Class I odorant receptors, TAS1R and TAS2R taste receptors, are markers for subpopulations of circulating leukocytes, Journal of leukocyte biology, vol.97, pp.533-545, 2015.
DOI : 10.1189/jlb.2a0714-331rr

URL : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5477889/pdf

, Dragon Software for Molecular Descriptor Calculation, 2014.

A. M. Waterhouse, J. B. Procter, D. M. Martin, M. Clamp, and G. J. Barton, Jalview Version 2-a multiple sequence alignment editor and analysis workbench, Bioinformatics, vol.25, pp.1189-1191, 2009.
DOI : 10.1093/bioinformatics/btp033

URL : https://academic.oup.com/bioinformatics/article-pdf/25/9/1189/526576/btp033.pdf

N. Eswar, B. Webb, M. A. Marti-renom, M. S. Madhusudhan, D. Eramian et al.,

A. Pieper and . Sali, Comparative protein structure modeling using Modeller, Curr Protoc Bioinformatics Chapter, issue.6, 2006.

O. Trott and A. J. Olson, AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading, J Comput Chem, vol.31, pp.455-461, 2010.

P. Schmidtke, A. Bidon-chanal, F. J. Luque, and X. Barril, MDpocket: open-source cavity detection and characterization on molecular dynamics trajectories, Bioinformatics, vol.27, pp.3276-3285, 2011.
DOI : 10.1093/bioinformatics/btr550

URL : https://academic.oup.com/bioinformatics/article-pdf/27/23/3276/16900891/btr550.pdf

M. A. Lomize, I. D. Pogozheva, H. Joo, H. I. Mosberg, and A. L. Lomize, OPM database and PPM web server: resources for positioning of proteins in membranes, Nucleic Acids Res, vol.40, pp.370-376, 2012.

S. Schrödinger, Release 2018-1: Maestro, LLC, 2018.

H. Zhuang and H. Matsunami, Evaluating cell-surface expression and measuring activation of mammalian odorant receptors in heterologous cells, Nature Protoc, vol.3, pp.1402-1413, 2008.

H. Zhuang and H. Matsunami, Synergism of accessory factors in functional expression of mammalian odorant receptors, J. Biol. Chem, vol.282, pp.15284-15293, 2007.

Y. R. Li and H. Matsunami, Activation state of the M3 muscarinic acetylcholine receptor modulates mammalian odorant receptor signaling, Sci. signal, vol.4, p.1, 2011.
DOI : 10.1126/scisignal.2001230

URL : http://europepmc.org/articles/pmc3034603?pdf=render

L. Buck and R. Axel, A novel multigene family may encode odorant receptors: a molecular basis for odor recognition, Cell, vol.65, pp.175-187, 1991.
DOI : 10.1016/0092-8674(91)90418-x

B. Malnic, J. Hirono, T. Sato, and L. B. Buck, Combinatorial receptor codes for odors, Cell, vol.96, pp.713-723, 1999.
DOI : 10.1016/s0092-8674(00)80581-4

URL : https://doi.org/10.1016/s0092-8674(00)80581-4

K. Touhara and L. B. Vosshall, Sensing odorants and pheromones with chemosensory receptors

, Annu. Rev. Physiol, vol.71, pp.307-332, 2009.

D. Kepchia, B. Sherman, R. Haddad, and C. W. Luetje, Mammalian odorant receptor tuning breadth persists across distinct odorant panels, PloS One, vol.12, p.185329, 2017.

Y. Yu, C. A. De-march, M. J. Ni, K. A. Adipietro, J. Golebiowski et al., Responsiveness of G protein-coupled odorant receptors is partially attributed to the activation mechanism, Proc. Natl. Acad. Sci. U. S. A, vol.112, pp.14966-14971, 2015.

X. Grosmaitre, S. H. Fuss, A. C. Lee, K. A. Adipietro, H. Matsunami et al., SR1, a mouse odorant receptor with an unusually broad response profile, J. Neurosci, vol.29, pp.14545-14552, 2009.

C. A. De-march, Y. Yu, M. J. Ni, K. A. Adipietro, H. Matsunami et al., Conserved Residues Control Activation of Mammalian G Protein-Coupled Odorant Receptors, J. Am. Chem. Soc, vol.137, pp.8611-8616, 2015.

J. Li, R. Haddad, S. Chen, V. Santos, and C. W. Luetje, A broadly tuned mouse odorant receptor that detects nitrotoluenes, J. Neurochem, vol.121, pp.881-890, 2012.

K. Nara, L. R. Saraiva, X. Ye, and L. B. Buck, A large-scale analysis of odor coding in the olfactory epithelium, J. Neurosci, vol.31, pp.9179-9191, 2011.

A. J. Venkatakrishnan, X. Deupi, G. Lebon, C. G. Tate, G. F. Schertler et al., Molecular signatures of G-protein-coupled receptors, Nature, vol.494, pp.185-194, 2013.

C. A. De-march, S. K. Kim, S. Antonczak, W. A. Goddard, and J. Golebiowski, G proteincoupled odorant receptors: From sequence to structure, Protein Sci, vol.24, pp.1543-1548, 2015.

J. P. Changeux and A. Christopoulos, Allosteric Modulation as a Unifying Mechanism for Receptor Function and Regulation, Cell, vol.166, pp.1084-1102, 2016.

N. Eswar, B. Webb, M. A. Marti-renom, M. S. Madhusudhan, D. Eramian et al.,

A. Pieper and . Sali, Comparative protein structure modeling using Modeller, Current protocols in bioinformatics Chapter, pp.5-6, 2006.

O. Trott and A. J. Olson, AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading, J. Comp. Chem, vol.31, pp.455-461, 2010.

G. Glusman, A. Bahar, D. Sharon, Y. Pilpel, J. White et al., The olfactory receptor gene superfamily: data mining, classification, and nomenclature, Mamm. Genome, vol.11, pp.1016-1023, 2000.

C. A. De-march, S. K. Kim, S. Antonczak, W. A. Goddard, and J. Golebiowski, G proteincoupled odorant receptors: from sequence to structure, Protein Sci, vol.24, pp.1543-1548, 2015.

C. A. De-march, J. Topin, E. Bruguera, G. Novikov, K. Ikegami et al., Odorant Receptor 7D4 Activation Dynamics, Angew. Chem. Int. Ed, vol.57, pp.4554-4558, 2018.

C. Geithe, J. Protze, F. Kreuchwig, G. Krause, and D. Krautwurst, Structural determinants of a conserved enantiomer-selective carvone binding pocket in the human odorant receptor OR1A1, Cell. Mol. Life Sci, vol.74, pp.4209-4229, 2017.

C. Bushdid, C. A. De-march, S. Fiorucci, H. Matsunami, and J. Golebiowski, Agonists of GProtein-Coupled Odorant Receptors Are Predicted from Chemical Features. The journal of physical chemistry letters 9, pp.2235-2240, 2018.

A. J. Venkatakrishnan, X. Deupi, G. Lebon, C. G. Tate, G. F. Schertler et al., Molecular signatures of G-protein-coupled receptors, Nature, vol.494, pp.185-194, 2013.

L. Charlier, J. Topin, C. A. De-march, P. C. Lai, C. J. Crasto et al., Molecular Modelling of odorant/olfactory receptor complexes, Methods Mol. Biol, vol.1003, pp.53-65, 2013.

N. Eswar, B. Webb, M. A. Marti-renom, M. S. Madhusudhan, D. Eramian et al.,

A. Pieper and . Sali, Comparative protein structure modeling using Modeller, Curr Protoc Bioinformatics Chapter, pp.5-6, 2006.

A. Patriksson, D. Van-der, and . Spoel, A temperature predictor for parallel tempering simulations, Phys. Chem. Chem. Phys, vol.10, pp.2073-2077, 2008.

D. R. Roe, T. E. Cheatham, ,. Ptraj, and C. , Software for Processing and Analysis of Molecular Dynamics Trajectory Data, J. Chem. Theory Comput, vol.9, pp.3084-3095, 2013.

P. Schmidtke, A. Bidon-chanal, F. J. Luque, and X. Barril, MDpocket: open-source cavity detection and characterization on molecular dynamics trajectories, Bioinformatics, vol.27, pp.3276-3285, 2011.

H. Saito, Q. Chi, H. Zhuang, H. Matsunami, and J. D. Mainland, Odor coding by a Mammalian receptor repertoire, Science signaling, vol.2, p.9, 2009.

J. D. Mainland, A. Keller, Y. R. Li, T. Zhou, C. Trimmer et al.,

W. L. Adipietro, H. Liu, S. Zhuang, S. S. Zhan, A. Lee et al., The missense of smell: functional variability in the human odorant receptor repertoire, Nat. Neurosci, vol.17, pp.114-120, 2014.

A. Keller, Philosophy of Olfactory Perception, 2016.

J. Lehrner, C. Eckersberger, P. Walla, G. Potsch, and L. Deecke, Ambient odor of orange in a dental office reduces anxiety and improves mood in female patients, Physiol. Behav, vol.71, pp.83-86, 2000.

A. Keller, R. C. Gerkin, Y. Guan, A. Dhurandhar, G. Turu et al., Predicting human olfactory perception from chemical features of odor molecules, Science, vol.355, pp.820-826, 2017.

A. Keller and L. B. Vosshall, Olfactory perception of chemically diverse molecules, BMC Neurosci, vol.17, p.55, 2016.

E. A. Krusemark, L. R. Novak, D. R. Gitelman, and W. Li, When the sense of smell meets emotion: anxiety-state-dependent olfactory processing and neural circuitry adaptation, J. Neurosci, vol.33, pp.15324-15332, 2013.

M. L. Loggia, M. Juneau, and M. C. Bushnell, Autonomic responses to heat pain: Heart rate, skin conductance, and their relation to verbal ratings and stimulus intensity, Pain, vol.152, pp.592-598, 2011.

E. Jang, B. Park, M. Park, S. Kim, and J. Sohn, Analysis of physiological signals for recognition of boredom, pain, and surprise emotions, J. Physiol. Anthropol, vol.34, p.25, 2015.