Biocrystallography and Modelling

Logo BioModThe BioMod team combines researchers with complementary expertise to study the structure-fonction relationships of biomolecules. On one hand, biostructure tools are used (NMR, X-Ray Diffraction, Homology Modelling, Molecular Dynamics) to determine the three-dimensional structure of enzymes and analyse their catalytic properties. On the other hand, original methods from multipolar charge density and ultra-high resolution crystallography are being developed in order to obtain accurate electrostatic properties of biomolecules. The development of these methods is done on the basis of MoProSuite program allowing the charge density refinement and MoProViewer which allows the visualisation of precise molecular properties and interactions. In close collaboration with biologists, biochemists and chemists, the team studies family of enzymes and small organic molecules with potential applications for health and in the field of agronomy.

Structure-function relationships

We are recognized for our ability to experimentally obtain three-dimensional structures ofbiomod_img9 biological macromolecules and to analyze their structure function relationships. A first research topic on which we have more than 10 years of expertise concerns glutathione transferases and their complexes with small ligands (read more…). A second one is focused on the characterization, at the molecular level and from a fundamental point of view, of the bacterial conjugation allowing these microorganisms to evolve rapidly, for example in order to resist an antibiotic (read more…). We also have an expertise in the analysis of the conformations of peptidomimetics in the solid state.

We determine the structures by X-ray crystallography or by NMR. Our crystallogenesis platform includes two pipetting robots and a semi-automatic binocular. It allows us to perform many tests and increases the chances of obtaining crystals. Thanks to the X-ray diffraction and scattering platform hosted by the laboratory, we can perform preliminary tests of the crystals at home, and even collect experimental data necessary to establish a preliminary structure. Our access to the SOLEIL and ESRF synchrotrons allows us to improve them at maximum resolution.

Molecular modelling at ultra high resolution

An extensive survey of Cambridge Structural Database is carried out to study thebiomod_img6 directionality and stereochemistry of hydrogen bonds with an oxygen acceptor including carbonyl, alcohols, phenols, ethers and esters groups. The results obtained through this survey are correlated with the charge density of these different chemical groups. The electron density of these different oxygen atoms types show striking dissimilarities in the electron lone pairs configuration.

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Software MoProSuite

The refinement program MoPro (Molecular Properties) is dedicated to the charge-densitybiomod_img8 refinement at (sub)atomic resolution of structures ranging from small molecules to biological macromolecules. MoPro uses the multipolar pseudo-atom model for the electron-density refinement. Alternative methods are also proposed, such as modelling bonding and lone-pair electron density by virtual spherical atoms.

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