<<

J. Golebiowski France Nice CNRS deNice deChimie Institut

-

Université Université Nice Vers -

Sophia AntipolisSophia

un NumeriNose nez Avec Jérôme Loic

Briand, CSGA INRA Dijon Golebiowski computationel Republic Deagu DGIST Brain

and

of of

Cognitive Korea

Défi S cience

INPHYNITY 2016

D

epartment

J. Golebiowski 2

J. Golebiowski 3

J. Golebiowski IN THE VARIANTS SENSE

AND INVARIANTSAND

OF SMELL

4

J. Golebiowski J. Golebiowski

J. Golebiowski 7

J. Golebiowski J. Golebiowski J. Golebiowski J. Golebiowski ~ Chemical 27.10

9

molecules

space

11

J. Golebiowski — science,measure smell. a youfind aIf areambitiousnew to youhave nocanof science anddifferences, Butuntilcantheirlikeness measure you rosesasafetida. upto manydifferentkinds smells, of is veryIt obviouswethat havevery between smellkinds andanother?of two Can youdifferencemeasurethe twiceanother?as strong Can youtell is smell just whetherone Did smell? ayou measureever theall from way the AlexanderBell, Graham

odour

1914 of violets violets of and odour

.

12

J. Golebiowski 13

J. Golebiowski J. Golebiowski J. Golebiowski

J. Golebiowski

(spicy) ethyl (herbaceous) isopropyl (musk) Musk ketone (musk) Adrostenol - dimethylfuranone

- methylfuranone

of of dimension ~396. An odorant can bedescribed as avector

17

J. Golebiowski chemistry are thuscompletelyknown, andthedifficulty liesonlyinthe fact that “The fundamental lawsnecessaryfor themathematicaltreatmentof[…]whole Paul Dirac application of theselawsleadsto equations thataretoo complextobesolved”

deorphanization of ORs Towards a computational -

1929

J. Golebiowski The computational microscope

19

J. Golebiowski confidentiel

CSGA, INRA Dijon Numerinose

Y Data Y Data 100 200 300 400 500 100 200 300 400 500 600 0 0 1 1 VV EC OR5P3 EC VV EC OR5P3 EC 50 50 = - µM = - µM 50 50 = 544.3µM 10 = 329.1µM 10 (+)-carvone [µM] (-)-carvone [µM] hOR5P3 hOR5P3

100 100 in vitro 1000 1000

data

20

J. Golebiowski Luciférase Luciférase 06/11/09

Normalized luciferase value Normalized luciferase value 10 20 30 40 50 60 10 15 20 25 10 12 14 10 12 14 0 0 5 0 2 4 6 8 0 2 4 6 8 1 1 1 1 EC50 = 34µM = EC50 10 10 10 10 Tetra decalactone [µM] decalactone Tetra Coffee difuran [µM] difuran Coffee (+) carvone [µM] (+) carvone 1-octanol [µM] 1-octanol 100 100 100 100

1000 1000 1000 1000 10 12 14 10 15 20 25 10 12 14 10 20 30 40 0 2 4 6 8 0 5 0 2 4 6 8 0 1 1 1 1 10 10 10 Butyl butyryl lactate [µM] lactate butyryl Butyl 10 Butyl formate [µM] Butyl (-) carvone [µM] carvone (-) Coumarine [µM] Coumarine 100 100 100 100 hOR5P3 (Normalized luciferase value) 1000 1000 1000 1000 10 12 14 10 12 14 10 12 14 10 20 30 40 50 0 2 4 6 8 0 2 4 6 8 0 2 4 6 8 0 1 1 1 1 EC50 = 47µM = EC50 trans, trans-2,4-undecadienal [µM] trans-2,4-undecadienal trans, 10 10 10 10 Quinoline [µM] Quinoline Benzene [µM] Benzene Eugenol [µM] Eugenol 100 100 100 100 1000 1000 1000 1000 10 12 14 10 12 14 10 12 14 10 15 0 2 4 6 8 0 2 4 6 8 0 2 4 6 8 0 5 0.1 1 1 1 hOR5P3 10 10 10 1 Cis-3-hexen-1-ol [µM] Cis-3-hexen-1-ol Androstenone [µM] Androstenone Celery ketone [µM] ketone Celery Citral [µM] Citral 100 100 100 10 1000 1000 1000 100

J. Golebiowski biomimetic computational Towards nose

a

J. Golebiowski 23

J. Golebiowski 24

J. Golebiowski OR2T27 OR10R2 OR2T29 OR2T33 OR2M4 OR8B12 OR2V1 OR8B4 OR8U9 OR8B3 OR8D4 OR52W1 OR1D5 OR8K1 OR9G4 OR5D3 OR52N4 OR5B17 OR5B3 OR13G1 OR52N1 OR52A1 OR52K2 OR3A2

OR51V1 OR1J4

OR7A5 OR51D1

OR5C1 OR5AS1

OR51F2 (

OR51G2 -

OR6V1 )

OR2B11 OR51A4 -

OR11H4 OR52B4 Carvone Carvone Activation Profile

OR52B2 OR11H12

OR5A2 OR51B4

OR56B1

O OR6T1

OR56A5 OR6S1

OR56A1 OR1M1

0,5 1,5 OR13C5

0 1 2

OR6A2 OR14A2 OR11L1 OR5AK3

OR8H2 OR6F1 OR6C76 OR6K6 OR11H6

OR10A5 OR9Q2

OR2L8

OR10H3 OR2L5

OR10H2 OR7G1

OR2A14

OR2AG1 OR10W1 OR2G3

OR6B1 OR10P1 OR2AK2

OR13D1 OR2W3

OR13C2

OR1A1 OR2F2

OR2J3 OR5T2

OR1K1 OR5K1 OR1B1

OR5H14 OR1L3

OR10G4

OR10S1 OR4D10 OR1E2 OR4D5 OR4K2 OR4F5

OR4F21 OR4N2 OR4K13 OR4K17

OR2M3 OR2M2 OR2T5 OR8G1 OR2T1 OR14C36 OR2V2 OR8G2 OR5M3 OR2T8 OR8B8 OR7D4 OR5B12 OR8J1 OR8K3 OR52L2 OR5B21 OR5AU1 OR52J3 OR52N2 OR7A10 OR52A5 OR52E6

OR1C1

OR51Q1

OR11A1 OR1J2

OR51E2

OR51L1 OR6B2

(+)

OR6Y1

OR51I1

OR51A7

OR9A2

OR52B6 - OR2C1

Carvone Carvone Activation Profile OR52H1

OR1I1

OR6Q1

OR11H1 OR52I1

OR51E1

OR56B4 OR9A4

OR10Q1

O OR56A4

OR2D3

0,5 1,5

0 1 2

OR10K1 OR5AX1 OR6C3 OR14J1 OR6C1 OR7D2 OR6C70 OR1S1 OR6N2 OR10A6

OR9Q1

OR7E24

OR10H4

OR2L13

OR6C4 OR7G2

OR2A5

OR2AG2

OR1J1 OR10A4

OR7A17 OR2C3

OR2W1 OR2K2

OR2AE1

OR13C9

OR5P3 OR2H1

OR4C15 OR13J1

OR1L4 OR5K2

OR10G3 OR5H15

OR1L1 OR5K3

OR12D2 OR4D1

OR4E2 OR4D9

OR4C3 OR4M2 OR4F3

OR4F17 OR4K14 OR4N5

J. Golebiowski OR2T27 OR10R2 OR2T29 OR2T33 OR2M4 OR2V1 OR8B12 OR8B4 OR8U9 OR8B3 OR8D4 OR52W1 OR1D5 OR8K1 OR9G4 OR5D3 OR52N4 OR5B17 OR5B3 OR13G1 OR52N1 OR52A1 OR3A2 OR52K2

OR51V1 OR1J4

OR7A5 OR51D1

OR5C1

OR5AS1

OR51F2 (

OR51G2

- OR6V1 )

OR2B11 OR51A4 -

OR11H4 OR52B4 Carvone Activation Profile

OR52B2 OR11H12

OR5A2 OR51B4

OR56B1 OR6T1

OR56A5 OR6S1

OR56A1 OR1M1

0,5 1,5 OR13C5

0 1 2 O

OR6A2 OR14A2 OR11L1 OR5AK3

OR8H2 OR6F1 OR6C76 OR6K6 OR11H6

OR10A5 OR9Q2

OR2L8

OR10H3

OR2L5

OR10H2 OR7G1

OR2A14

OR2AG1 OR10W1 OR2G3

OR6B1 OR10P1 OR2AK2

OR13D1 OR2W3

OR13C2

OR1A1 OR2F2

OR2J3 OR5T2

OR1K1 OR5K1 OR1B1

OR5H14

OR1L3 OR10G4

OR10S1 OR4D10 OR1E2 OR4D5 OR4K2 OR4F5

OR4F21 OR4N2 OR4K13 OR4K17

OR2T27 OR10R2 OR2T29 OR2T33 OR2M4 OR8B12 OR2V1 OR8B4 OR8U9 OR8B3 OR8D4 OR52W1 OR1D5 OR8K1 OR9G4 OR5D3 OR52N4 OR5B17 OR5B3 OR13G1 OR52N1 OR52A1 OR52K2 OR3A2

OR51V1

OR1J4

OR7A5 OR51D1

OR5C1 OR5AS1 ( OR51F2

-

OR51G2 )

OR6V1 OR2B11 OR51A4 -

Menthone

OR11H4 OR52B4

OR52B2 OR11H12

OR5A2 OR51B4

OR56B1

OR6T1 OR56A5

OR6S1 OR56A1

OR1M1

0,5 1,5 OR13C5

0 1 2

Activation Activation Profile

O OR6A2 OR14A2 OR11L1 OR5AK3

OR8H2 OR6F1 OR6C76 OR6K6 OR11H6

OR10A5 OR9Q2 OR2L8

OR10H3

OR2L5

OR10H2 OR7G1

OR2A14 OR2AG1

OR10W1 OR2G3

OR6B1

OR10P1 OR2AK2 OR13D1

OR2W3 OR13C2

OR1A1

OR2F2

OR2J3 OR5T2 OR1K1 OR5K1

OR1B1 OR5H14

OR1L3 OR10G4

OR10S1

OR4D10

OR1E2 OR4D5 OR4K2 OR4F5 OR4F21 OR4N2 OR4K13 OR4K17

J. Golebiowski • https://numerinose.wordpress.com

partenaires

27