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Ligand-Receptor Interactions Involved in Chemical Senses. Insights From Défi INPHYNITY 2016 J. Golebiowski J. NumeriNose Vers un nez computationel Jérôme Golebiowski Avec Loic Briand, CSGA INRA Dijon Institut de Chimie de Nice Brain and Cognitive Science Department CNRS - Université Nice - Sophia Antipolis DGIST Nice Deagu France Republic of Korea J. Golebiowski 2 J. Golebiowski 3 J. Golebiowski J. VARIANTS AND INVARIANTS IN THE SENSE OF SMELL 4 J. Golebiowski J. Golebiowski J. Golebiowski 7 J. Golebiowski J. Golebiowski J. Golebiowski Chemical space ~ J. Golebiowski J. 9 27.10 molecules 11 Did you ever measure a smell? J. Golebiowski J. Can you tell whether one smell is just twice strong as another? Can you measure the difference between two kinds of smell and another? It is very obvious that we have very many different kinds of smells, all the way from the odour of violets and roses up to asafetida. But until you can measure their likeness and differences, you can have no science of odour. If you are ambitious to find a new science, measure a smell. —Alexander Graham Bell, 1914 12 J. Golebiowski 13 J. Golebiowski J. Golebiowski J. Golebiowski J. Golebiowski J. Adrostenol (musk) Musk ketone (musk) isopropyl-methylfuranone (herbaceous) ethyl-dimethylfuranone (spicy) An odorant can be described as a vector of dimension ~396. 17 Towards a computational J. Golebiowski J. deorphanization of ORs “The fundamental laws necessary for the mathematical treatment of […] the whole of chemistry are thus completely known, and the difficulty lies only in the fact that application of these laws leads to equations that are too complex to be solved” Paul Dirac - 1929 The computational microscope J. Golebiowski J. 19 Numerinose in vitro data J. Golebiowski J. hOR5P3 500 OR5P3 EC50 = 544.3µM VV EC50 = - µM 400 300 Y Data Y 200 100 0 1 10 100 1000 (-)-carvone [µM] hOR5P3 confidentiel 600 OR5P3 EC50 = 329.1µM VV EC50 = - µM 500 400 300 Y Data Y 200 100 0 1 10 100 1000 (+)-carvone [µM] CSGA, INRA Dijon 20 hOR5P3 hOR5P3 (Normalized luciferase value) 60 40 50 EC50 = 34µM EC50 = 47µM 50 15 30 40 40 30 30 20 10 20 20 10 J. Golebiowski J. 10 5 10 0 0 0 0 1 10 100 1000 1 10 100 1000 1 10 100 1000 1 10 100 1000 (+) carvone [µM] Coumarine [µM] Quinoline [µM] Cis-3-hexen-1-ol [µM] 14 14 14 14 12 12 12 12 Normalized luciferase value 10 10 10 10 8 8 8 8 6 6 6 6 4 4 4 4 2 2 2 2 0 0 0 0 1 10 100 1000 1 10 100 1000 1 10 100 1000 0.1 1 10 100 Coffee difuran [µM] Butyl formate [µM] Benzene [µM] Androstenone [µM] 14 25 14 14 12 12 12 20 10 10 10 8 15 8 8 6 6 6 10 4 4 4 2 5 2 2 0 0 0 0 1 10 100 1000 1 10 100 1000 1 10 100 1000 1 10 100 1000 1-octanol [µM] (-) carvone [µM] Eugenol [µM] Citral [µM] 25 14 14 14 Normalized luciferase value 12 12 12 20 10 10 10 15 8 8 8 6 6 6 10 4 4 4 5 2 2 2 0 0 0 Luciférase0 06/11/09 1 10 100 1000 1 10 100 1000 1 10 100 1000 1 10 100 1000 Tetra decalactone [µM] Butyl butyryl lactate [µM] trans, trans-2,4-undecadienal [µM] Celery ketone [µM] J. Golebiowski J. Towards a biomimetic computational nose J. Golebiowski 23 J. Golebiowski 24 (-)-Carvone Activation Profile (+)-Carvone Activation Profile OR51E1OR56B4OR56A4 OR5AX1OR14J1OR7D2 J. Golebiowski J. OR52H1OR52I1 OR1S1OR10A6 OR13C5 OR51A7OR52B6 OR7E24 OR51B4OR56B1OR56A5OR56A1 OR14A2OR5AK3OR6F1OR6K6 OR51I1 2 OR2L13OR7G2 OR52B4OR52B2 OR10A5OR2L8 OR51L1 OR2AG2 OR51G2OR51A4 2 OR2L5 OR51E2 OR10A4 OR51F2 OR7G1OR2AG1 OR51Q1 OR2C3 OR51V1OR51D1 OR2G3 OR52E6 OR2K2 OR52K2 OR10P1 OR52A5 1,5 OR13C9 OR52A1 OR13D1 OR52N2 OR2H1 OR52N1 1,5 OR13C2 OR52J3 OR13J1 OR52N4 OR2F2 OR52L2 OR5K2 OR52W1 OR5T2 OR14C36 1 OR5H15 OR5D3 OR5K1 OR7D4 OR5K3 OR1D5 1 OR5H14 OR8B8 OR10G4 OR4D1 OR8B12 OR8G2 OR4D9 OR8B3 OR4D10 OR8G1 0,5 0,5 OR4D5 OR4M2 OR8B4 OR2M2 OR4F17 OR10R2 OR4F5 OR2T5 OR2T29 OR4N2 0 OR4N5 OR4K17 OR2M3 OR4K14 OR2T27 0 OR2T1 OR2M4 OR4K13 OR4F3 OR4F21 OR2V2 OR4C3 OR2V1 OR2T8 OR2T33 OR4K2 OR4E2 OR8U9 OR1E2 OR5M3 OR12D2 OR8D4 OR10S1 OR8J1 OR1L1 OR8K1 OR1L3 OR8K3 OR10G3 OR9G4 OR1B1 OR5B12 OR1L4 OR5B3 OR1K1 OR5B21 OR4C15 OR5B17 OR2J3 OR5AU1 OR5P3 OR13G1 OR1A1 OR7A10 OR2AE1 OR2W3 OR1C1 OR2W1 OR3A2 OR2AK2 OR1J2 OR7A17 OR1J4 OR6B1 OR11A1 OR1J1 OR7A5OR5C1 OR10W1 OR6B2 OR2A5 OR5AS1 OR2A14 OR6Y1OR9A2 OR6C4 OR6V1OR2B11 OR10H3OR10H2 OR2C1 OR9Q1OR10H4 OR11H4OR5A2 OR11H6OR9Q2 OR1I1OR6Q1OR11H1 OR6C70OR6N2 OR11H12OR6T1OR6S1OR1M1 OR6A2OR11L1OR8H2OR6C76 OR9A4OR10Q1OR2D3 OR10K1OR6C3OR6C1 O O (-)-Carvone Activation Profile (-)-Menthone Activation Profile OR13C5 OR51B4OR56B1OR56A5OR56A1 OR14A2OR5AK3OR6F1 OR52B4OR52B2 OR6K6OR10A5 OR13C5 J. Golebiowski J. OR51A4 OR2L8 OR51G2 2 OR2L5 OR56B1OR56A5OR56A1 OR14A2OR5AK3OR6F1 OR51F2 OR7G1OR2AG1 OR52B4OR52B2OR51B4 OR6K6OR10A5 OR51V1OR51D1 OR2G3 OR51G2OR51A4 OR2L8OR2L5 OR52K2 OR10P1 OR51F2 2 OR7G1 OR13D1 OR51D1 OR2AG1OR2G3 OR52A1 1,5 OR13C2 OR51V1 OR10P1 OR52N1 OR2F2 OR52K2 OR13D1 OR52N4 OR52A1 1,5 OR13C2 OR52W1 OR5T2 OR52N1 OR2F2 OR5D3 1 OR5K1 OR52N4 OR5T2 OR1D5 OR5H14 OR52W1 OR10G4 OR5D3 OR5K1 OR8B12 OR1D5 1 OR5H14 OR8B3 OR4D10 OR8B12 OR10G4 OR8B4 0,5 OR4D5 OR8B3 OR4D10 OR10R2 OR4F5 OR8B4 0,5 OR4D5 OR2T29 OR4N2 OR10R2 OR4F5 OR2T27 0 OR4K17 OR2T29 OR4N2 OR2M4 OR4K13 OR2T27 0 OR4K17 OR2V1 OR4F21 OR2M4 OR4K13 OR2T33 OR4K2 OR2V1 OR4F21 OR8U9 OR1E2 OR2T33 OR4K2 OR8D4 OR10S1 OR8U9 OR1E2 OR1L3 OR8D4 OR10S1 OR8K1 OR1B1 OR1L3 OR9G4 OR8K1 OR1B1 OR5B3 OR1K1 OR9G4 OR1K1 OR5B17 OR2J3 OR5B3 OR2J3 OR13G1 OR1A1 OR5B17 OR1A1 OR3A2 OR2W3 OR13G1 OR2W3 OR1J4 OR2AK2 OR3A2 OR2AK2 OR7A5 OR6B1 OR1J4 OR6B1 OR5C1 OR2A14OR10W1 OR7A5OR5C1 OR10W1 OR5AS1OR6V1 OR10H2 OR5AS1 OR2A14 OR2B11 OR9Q2OR10H3 OR6V1 OR10H3OR10H2 OR11H4OR5A2 OR6C76OR11H6 OR2B11OR11H4 OR11H6OR9Q2 OR11H12OR6T1OR6S1OR1M1 OR6A2OR11L1OR8H2 OR11H12OR5A2OR6T1OR6S1OR1M1 OR6A2OR11L1OR8H2OR6C76 O O partenaires J. Golebiowski J. • https://numerinose.wordpress.com 27 .
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