Research : ligand -receptor interactions at the atomic level.
Molecular Modeling, Computational Chemistry
I mainly use molecular modeling techniques, going from quantum mechanical calculations (using for example the Gaussian package) to MM and QM/MM Molecular Dynamics simulations (mainly using the Amber and NAMD packages). My reseach projects are focused on ligand-receptor systems study. They are centered on the description of the molecular basis of the chemical senses, and more particularly the sense of smell (See the AROMAGRI Group).
Ongoing funded projects :
The project OLFACTOME (launched in 2011) plans to propose a new definition of Structure-Odour Relationships, with the explicit take into account for the human olfactory receptors. It is labellized by the competitiveness cluster PASS (Parfums Arômes Senteurs Saveurs.
The project PROTANIN aiming at studying protein - tannins interactions (notably trigerring astringency, a sense involved in taste) has been funded by the National Research Agency (ANR in french) for the period 2007-2010. The projet involves biochemistry (INRA Montpellier), NMR spectroscopy
(CBS, Montpellier), X-Ray scattering spectroscopy (ESPCI, Paris) and
Molecular Modeling techniques (University of Nice).
Our project dedicated to propose electronic courses on Molecular Modeling techniques has been funded by UNISCIEL (2008). Unisciel plans to gather various courses on the web, more particularly
focused on scientific topics (Mathematics, Physics, Chemistry, etc.)
Our project dedicated to propose electronic courses on Quantum Chemistry has been funded by UNISCIEL (2009).
the project HYLIOX has been funded by the french ANR for the period 2007-2010. It plans to produce photosynthetic hydrogen by protein engeeniering.
The sense of smell
Although,
much progress has been made towards understanding the molecular basis
of olfactory perception, many questions remain unanswered. We mainly
use various computational approaches to gain informations on the
mechanistic event underlying perception of odors. Molecular dynamics
simulations are for example preformed to understand the atomic-level
properties of Odorant Binding Proteins and Olfactory Receptors.
In the following, you will find general informations on the sense of smell.
The chemical senses at the molecular level
From a molecule to an odour (movie, ~8 minutes).
Chemoreception
is the aptitude of living organisms to identify chemical compounds in
their environment and to evaluate their concentration.Olfaction is
initiated by a molecular interaction of chemicals called odorants with
olfactory neurons located in the epithelium of the nasal cavity. see our 3D movie, from a molecule to an odour in a separate page.
U. Meierhenrich, J. Golebiowski, X. Fernandez and D. Cabrol-Bass. The molecular basis of olfactory chemoreception. Angew. Chem. Int. Ed. Engl. 43 (2004) 6410-12
U. Meierhenrich, J. Golebiowski, X. Fernandez et D. Cabrol-Bass. De la molécule à l'odeur. L'Actualité Chimique, septembre 2005 (in french)
Glomerules
belong to the part of the brain that collects informations brought by
Olfactory Neuron activation. The neuron cilia project down out of the
olfactory epithelium into an aqueous layer, preventing them from drying
out: the olfactory mucus (yellow waves).
On the surface of these neurons, the signal is transmitted when an olfactory receptor is activated by an odorant.
Click on the bottom of the small box at the left (ooo), you'll see how an odorant mixture signal is decomposed by the neurons and their correponding glomerules.
The
small circles (the odorants) generally activate a given type of neuron,
but the specificity is low, so that a "green" odorant can activate a
"blue" neuron. You can see it by clicking on the "green-blue" mixture (oo), or only the pure green odorants(o).
This lack of selectivity endows the system a spectacular discriminatory power, able to perceive many thousands of odors.
............
An olfactory receptor (ribbon) placed
within a lipid bilayer (blue) and solvated by
water (red)
The Olfactory Receptors
On
the surface of the olfactory neurons, the activation of Olfactory
Receptors, a class of protein belonging to the GPCR family and
dedicated to transmit the signals to the brain, originates odour
perception. Humans share ~ 1000 types of ORs, of which ~ 300 are
considered to be functional. The biological method of chemical
recognition is far removed from the simple "lock and key" analogy,
since a single OR can be activated by multiple odorants, and that a
single odorant can activate several ORs.
Generally,
three-dimensional protein structures can be determined through direct
measurements by X-ray crystallography, electron microscopy, and NMR
spectroscopy. These techniques are, however, suitable only for
water-soluble proteins, and not for GPCR, which require precisely
balanced physicochemical conditions for structural and functional
integrity. As such conditions are difficult to achieve, new techniques,
such as two-dimensional cryomicroscopy, have to be employed to attempt
the elucidation of these structures. Therefore, the amount of
experimental information available on the three-dimensional structure
of GPCR is limited. So far, only the rhodopsin GPCR structure has been
determined by direct measurements. Concerning ORs, few structures have
been determined by means of computational approaches.
The Odorant Binding Proteins
Prior
to their interaction with ORs, odorants are associated with Odorant
Binding Proteins (OBPs) present in the olfactory mucus. OBPs belong to
a class of carrier proteins present in physiological fluids. They are
though to contribute actively to the transport of the odorant from the
inhaled air stream through the mucus to the cilia of the olfactory
neurons. The role of these OBPs stills need to be explored in details.
L.
Charlier, D. Cabrol-Bass, J. Golebiowski . How does human odorant
binding protein bind odorants ? The case of aldehydes studied by
molecular dynamics. C.R Chimie, 2009, 12, 905-910
L.
Charlier, C. Nespoulous, S. Fiorucci, S. Antonczak and J. Golebiowski:
Binding free energy prediction in strongly hydrophobic systems,
PhysChemChemPhys, 2007, 9 , 5761-5771
J. Golebiowski, S. Antonczak, S. Fiorucci, D. Cabrol-Bass: Molecular
mechanism underlying Odorant Binding Protein chemoreception .
PROTEINS: Structure, Function, and Bioinformatics, 2007 , 67,
448-458
J.
Golebiowski, S. Antonczak, D. Cabrol-Bass: Molecular dynamics studies
of odorant binding protein free of ligand and complexed to pyrazine and
octenol. Journal of Molecular Structure THEOCHEM, 763, 2006 , 165-174
Cours "Chimie structurale. Prédiction de propriétés phisico-chimiques" L1S2-SM
Cours "Drug design" , 3ieme année Génie Biologique à l'Ecole Polytechnique
Universitaire de Nice
Cours "Drug design", Master 1 & 2 Pharmacologie
Cours et TD "Modelisation Moléculaire", Licence 3 - Chimie
Articles
2012
J. Golebiowski, X. Fernandez. Chimie des substances odorantes. Introduction sur la chimie des composés odorants, notions de physico-chimie, grandes classes substances odorantes, notion de seuil de perception, généralités de la physiologie de l’olfaction. Chapitre 1.1 15 pages in «Les Huiles Essentielles. Tradition et Innovation». Dunod. Ed. 2012
2011
L. Charlier, C. Crasto, J. Golebiowski Chap. XX. Molecular Modeling of Olfactory Receptors. 10 pages in “Methods in Molecular Biology. Olfactory Receptors” Humana Press.Ed. 2011. in press
M.Maïbèche, JM. Heydel, AM. Le Bon, J. Golebiowski, L. Briand Chap. 3.2. Périrécéption et protéines porteuses (Perireception and Odorant Binding Proteins) 9 pages in “ODORAT et GOUT : de la neurobiologie des sens chimiques aux applications agronomiques, industrielles et médicales” (380 pages), QUAE Ed. 2011. in press.
J. Golebiowski, S. Fiorucci, M. Adrian-Scotto, J. Fernandez-Carmona, S. Antonczak Molecular features underlying the perception of astringency as probed by molecular modeling. Molecular informatics, 2011, 30, 410-414
2010
S. Fiorucci, S. Antonczak, J. Golebiowski. Prediction/calculation of protein-protein binding affinities and mutation effects, Chapter 11, inProtein-proteincomplexes:Analysis, modelling and drug design. M. Zacharias Ed. imperial Press 2010.
C. Roucairol, S. Azoulay, M.C. Nevers, J. Golebiowski, C. Créminon, J. Grassi, A. Burger, D. Duval. Design, synthesis and studies of triphosphate analogues for the production of anti AZT-TP antibodies. Bioorganic & Medicinal Chemistry Letters, 2010, 20,987-990
2009
L. Charlier, D. Cabrol-Bass, J. Golebiowski . How does human odorant binding protein bind odorants ? The case of aldehydes studied by molecular dynamics. C.R Chimie, 2009, 12, 905-910
S. Antonczak, S. Fiorucci, J. Golebiowski, D. Cabrol-Bass. Theoretical investigations of the role played by Quercetinase Enzymes upon flavonoids oxygenolsysis mechanism. PhysChemChemPhys,2009, 11, 1491-1501
2008
L. Charlier, S. Antonczak, E. Jacquin-joly, D. Cabrol-Bass, J. Golebiowski. Deciphering the selectivity of Bombyx mori pheromone binding protein for bombykol over bombykal. A theoretical approach. ChemPhysChem 2008,9, 2785-2793
S. Fiorucci ; J. Golebiowski; D. Cabrol-Bass; S. Antonczak . Molecular Simulations enlighten the binding mode between quercetine and lipoxygenase-3. PROTEINS : Structure, Function, and Bioinformatics, 2008,73, 290-298
2007
L. Charlier; C. Nespoulous, S. Fiorucci, S. Antonczak; J. Golebiowski Binding free energy prediction in strongly hydrophobic systems. Physical Chemistry Chemical Physics, 2007,9,5761-5771 .
S. Fiorucci ; J. Golebiowski; D. Cabrol-Bass; S. Antonczak . Molecular Simulations bring new insights into Flavonoid/Quercetinase Interaction Modes. PROTEINS: Structure, Function, and Bioinformatics, 2007, 67, 961-970
J. Golebiowski, S. Antonczak, S. Fiorucci, D. Cabrol-Bass Molecular mechanism underlying Odorant Binding Protein chemoreception. PROTEINS: Structure, Function, and Bioinformatics, 2007, 67, 448-458
S. Fiorucci ; J. Golebiowski; D. Cabrol-Bass; S. Antonczak. DFT Study of Quercetin Activated Forms Involved in Antiradical, Antioxidant, and Prooxidant Biological Processes. Journal of Agricultural Food and Chemistry, 2007, 55, 903-911
F. Berrue, O. P. Thomas, R. Laville, S. Prado, J. Golebiowski, R. Fernandez and P. Amade The marine sponge Plakortis zyggompha: a source of original bioactive polyketides. Tetrahedron, 2007, 63, 2328-2334
2006
S. Antoniotti, J. Golebiowski, D. Cabrol-Bass, E. Dunach Density functional theory investigations on acid-catalysed epoxide oxidative ring-opening by DMSO. Competition between oxidation processes. Journal of Molecular Structure THEOCHEM, 763, 2006 155-159
S. Fiorucci, J. Golebiowski, D. Cabrol-Bass, S. Antonczak Molecular Simulations reveal a new entry site in Quercetin 2,3-Dioxygenase. A pathway for dioxygen? PROTEINS: Structure, Function, and Bioinformatics, 64, 2006, 845-850
J. Golebiowski, S. Antonczak, D. Cabrol-Bass Molecular dynamics studies of odorant binding protein free of ligand and complexed to pyrazine and octenol. Journal of Molecular Structure THEOCHEM, 763, 2006, 165-174
2005
U.J. Meierhenrich, J. Golebiowski, X. Fernandez, D. Cabrol-Bass De la molécule à l'odeur. (From a molecule to an odour) L'Actualité Chimique, septembre 2005, 29-40
2004
U.J. Meierhenrich, J. Golebiowski, X. Fernandez, D. Cabrol-Bass The molecular basis of olfactory chemoreception. Angew. Chem. Int. Ed. Engl. 43, 2004, 6410-6412; Angew. Chem. 116, 2004, 6570-6573
J. Golebiowski, S. Antonczak, J. Fernandez-Carmona, R. Condom, D. Cabrol-Bass Closing loop base pairs in RNA loop-loop complexes. Structural behaviour, interaction energy and solvation analysis through molecular dynamics simulations. Journal of Molecular Modeling , 10, 2004, 408-417
S. Antoniotti, S. Antonczak, J. Golebiowski Acid-Catalysed Oxidative Ring-Opening of Epoxide by DMSO. Theoretical Investigations on the Effect of Acid Catalysts and Substituents.Theoretical Chemistry Account, 112, 2004, 290 - 297
S. Fiorucci, J. Golebiowski, D. Cabrol-Bass, S. Antonczak Oxygenolysis of Flavonoid compounds. DFT Description of the Mechanism for Quercetin ChemPhysChem 2004, 5,1726-1733
J. Golebiowski, S. Antonczak, A. di-Giorgio, R. Condom, D. Cabrol-Bass Molecular Dynamics Simulation of Hepatis C Virus IRES IIId Domain : Structural Behaviour, Electrostatic and energetic Analysis. Journal of Molecular Modeling, 10, 2004, 60-68
2002
Golebiowski, J.; Lamare, V.; Ruiz-Lopez, M. F. Rb/Cs selectivity between Benzo21crown7 and riBenzo21Crown7. An ab initio study. Journal of Computational Chemistry 2002, 23(7), 724-731
Golebiowski, J.; Lamare, V.; Ruiz-Lopez, M. F. Quantum mechanical calculations on alkali complexes, in Calix2001. Chap. 18. Z. Asfari; V. Böhmer; J.M. Harrowfield; J. Vicens eds. Kluwer Academic, Dordrecht. 2002
2001
Lamare, V.; Golebiowski, J.; Martins-Costa, M.T.C.; Millot, C.; Ruiz-Lopez, M.F. Modélisation d'un calixarène-Couronne-6 et de ses Complexes Alcalins par Méthode Hybride Mécanique Quantique / Mécanique Moléculaire. Rapport Scientifique CEA/DCC 1999 2001,102-109
Lamare, V.; Haubertin, D.; Golebiowski, J.; Dozol, J. F. Molecular dynamics study of 21C7 crown ether derivatives and their alkali cations complexes. Comparison with 1,3-alt-calix[4]arenes-crown-6. Journal of Chemical Society, Perkin transaction 2 2001,1,121
Golebiowski, J.; Lamare, V.; Martins-Costa, M. T. C.; Millot, C.; Ruiz-Lopez, M. F. Role of electronic polarization on the liquid phase affinity of calixarene-crown ethers towards alkali cations. A QM/MM molecular dynamics simulation. Chemical Physics 2001,272,47-59
