VLDP web server: a powerful geometric tool for analysing protein structures in their environment.

International audienceProtein structures are an ensemble of atoms determined experimentally mostly by X-ray crystallography or Nuclear Magnetic Resonance. Studying 3D protein structures is a key point for better understanding protein function at a molecular level. We propose a set of accurate tools, for analysing protein structures, based on the reliable method of Voronoi-Laguerre tessellations. The Voronoi Laguerre Delaunay Protein web server (VLDPws) computes the Laguerre tessellation on a whole given system first embedded in solvent. Through this fine description, VLDPws gives the following data: (i) Amino acid volumes evaluated with high precision, as confirmed by good correlations with experimental data. (ii) A novel definition of inter-residue contacts within the given protein. (iii) A measure of the residue exposure to solvent that significantly improves the standard notion of accessibility in some cases. At present, no equivalent web server is available. VLDPws provides output in two complementary forms: direct visualization of the Laguerre tessellation, mostly its polygonal molecular surfaces; files of volumes; and areas, contacts and similar data for each residue and each atom. These files are available for download for further analysis. VLDPws can be accessed at http://www.dsimb.inserm.fr/dsimb_tools/vldp

Engineering an artificial pathway for Cis-Α-irone biosynthesis

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Engineering an artificial pathway for Cis-alpha-irone biosynthesis

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GÖÇ VE YAŞAM

Uluslararası Bakalorya Programı, A1 dersi Türk Dili ve Edebiyatı alanında ele alınan bu tezde, Orhan Kemal'in Gurbet Kuşları adlı yapıtında göç olgusu nedenleri ve sonuçlarıyla beraber incelenmiştir. Göç olgusuyla değişen toplumsal yapı, ekonomik ve kültürel farklılıklar çerçevesinde değerlendirilmiştir. Bu tezin amacı, göç olgusunun toplumsal yapıda alt sınıf ve üst sınıflardaki bireyler üzerindeki etkilerini ortaya koymaktır. Üç ana bölümden oluşan tezin ilk bölümünde yapıta adını veren Gurbet Kuşları kavramı üzerinde durulmuştur. Köylülerin aidiyetsizliği ve uyum sorunu bu bölümde aktarılmıştır. Tezin ikinci bölümünde ise köylülerin köyden kente göç sürecinde yaşadıkları kadın ve erkek figürler üzerinden neden ve sonuçlarıyla işlenmiştir. Tezin üçüncü bölümünde şehirliler başlığı altından genel olarak şehirde – İstanbul – yaşayan insanların göç sürecinde köylülerle yaşadıkları uyumsuzluk ve çatışmalara yer verilmektedir. Çalışmada göç sürecinde şehre yerleşen figürlerin şehirlilerle aralarındaki ekonomik ve kültürel farklılıkların sınıflar arasında geçişe olanak tanımadığı sonucuna varılmıştır

Controlling enantioselectivity of limonene synthases by exploring natural diversity combined to molecular engineering

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Topologie des macromolécules en interaction (analyse structurale des protéines à l'aide des diagrammes de Voronoï et Laguerre)

Les protéines sont des macromolécules essentielles dans le fonctionnement des cellules. Leurs structures sont gouvernées par des interactions entre résidus, unités fondamentales des protéines dont les spécificités proviennent de leur chaîne latérale. Connaissant la position des résidus dans l'espace, il est possible de représenter les protéines sous forme de graphes. Le diagramme de Voronoï, et son dual, le diagramme de Delaunay, ont été montrés pertinents pour l'analyse structurale de ces macromolécules. J'ai développé VLDP (Voronoï Laguerre Delaunay Protein), un programme d'analyses topologiques pour l'étude des protéines à l'aide de ces diagrammes. VLDP a été utilisé pour étudier les volumes des résidus et leurs contacts dans les protéines globulaires, ce sujet est d'intérêt pour aider à la compréhension du repliement des protéines. Pour comprendre le mécanisme de transport du fer à travers FepA, VLDP a été utile pour analyser le réseau d'eau à travers cette protéine membranaire.Proteins are biological macromolecules and essential in the cell function. Their structures are governed by interactions between residues, fundamental unities of proteins with specificities coming from their side chain. From space positions of residues, protein can be described by building of a graph. The Voronoï diagram and its dual, the Delaunay diagram, have been shown relevant to analyze the structures of these macromolecules. I have developed VLDP (Voronoï Laguerre Delaunay Protein), a program for topological analyses to study proteins, by using these diagrams. VLDP has been used to study the residue volumes and their contacts inner globular proteins, this topic is interesting in the understanding of protein folds. In order to understand the transport mechanism of iron through FepA, VLDP has been applied to analyze the water network crossing this membrane protein.CERGY PONTOISE-BU Neuville (951272102) / SudocSudocFranceF

Comparative Analysis of Protein -Protein Interface Methods

International audienceIn the cells, proteins are never alone. All proteins interact with other molecules to become functional. Protein-Protein interactions (PPIs) are essential for a broad range of cellular processes including signal transduction, cell-to-cell communication, transcription, replication, and membrane transport. So, studying PPIs is crucial to better understand the relationship between different protein partners and their functions. These interactions result in physical contacts of high specificity as a result of biochemical events steered by electrostatic forces including hydrophobic effect. Residues close in space determine protein contacts and computational approaches finding these residues are interesting for PPI studies

Combining multi-scale modelling methods to decipher molecular motions of a branching sucrase from glycoside-hydrolase family 70

Among alpha-transglucosylases from Glycoside-Hydrolase family 70, the Delta N-123-GB-CD2 enzyme derived from the bifunctional DSR-E from L. citreum NRRL B-1299 is particularly interesting as it was the first described engineered Branching Sucrase, not able to elongate glucan polymers from sucrose substrate. The previously reported overall structural organization of this multi-domain enzyme is an intricate U-shape fold conserved among GH70 enzymes which showed a certain conformational variability of the so-called domain V, assumed to play a role in the control of product structures, in available X-ray structures. Understanding the role of functional dynamics on enzyme reaction and substrate recognition is of utmost interest although it remains a challenge for biophysical methods. By combining long molecular dynamics simulation (1 mu s) and multiple analyses (NMA, PCA, Morelet Continuous Wavelet Transform and Cross Correlations Dynamics), we investigated here the dynamics of Delta N-123-GB-CD2 alone and in interaction with sucrose substrate. Overall, our results provide the detailed picture at atomic level of the hierarchy of motions occurring along different timescales and how they are correlated, in agreement with experimental structural data. In particular, detailed analysis of the different structural domains revealed cooperative dynamic behaviors such as twisting, bending and wobbling through anti- and correlated motions, and also two structural hinge regions, of which one was unreported. Several highly flexible loops surrounding the catalytic pocket were also highlighted, suggesting a potential role in the acceptor promiscuity of Delta N-123-GBD-CD2. Normal modes and essential dynamics underlined an interesting two-fold dynamic of the catalytic domain A, pivoting about an axis splitting the catalytic gorge in two parts. The comparison of the conformational free energy landscapes using principal component analysis of the enzyme in absence or in presence of sucrose, also revealed a more harmonic basin when sucrose is bound with a shift population of the bending mode, consistent with the substrate binding event

Modeling Protein Complexes and Molecular Assemblies Using Computational Methods

International audienceMany biological molecules are assembled into supramolecular complexes that are necessary to perform functions in the cell. Better understanding and characterization of these molecular assemblies are thus essential to further elucidate molecular mechanisms and key protein-protein interactions that could be targeted to modulate the protein binding affinity or develop new binders. Experimental access to structural information on these supramolecular assemblies is often hampered by the size of these systems that make their recombinant production and characterization rather difficult. Computational methods combining both structural data, molecular modeling techniques, and sequence coevolution information can thus offer a good alternative to gain access to the structural organization of protein complexes and assemblies. Herein, we present some computational methods to predict structural models of the protein partners, to search for interacting regions using coevolution information, and to build molecular assemblies. The approach is exemplified using a case study to model the succinate-quinone oxidoreductase heterocomplex

Combining multi-scale modelling methods to decipher molecular motions of a branching sucrase from glycoside-hydrolase family 70

<div><p>Among α-transglucosylases from Glycoside-Hydrolase family 70, the ΔN₁₂₃-GB-CD2 enzyme derived from the bifunctional DSR-E from <i>L</i>. <i>citreum</i> NRRL B-1299 is particularly interesting as it was the first described engineered Branching Sucrase, not able to elongate glucan polymers from sucrose substrate. The previously reported overall structural organization of this multi-domain enzyme is an intricate U-shape fold conserved among GH70 enzymes which showed a certain conformational variability of the so-called domain V, assumed to play a role in the control of product structures, in available X-ray structures. Understanding the role of functional dynamics on enzyme reaction and substrate recognition is of utmost interest although it remains a challenge for biophysical methods. By combining long molecular dynamics simulation (1μs) and multiple analyses (NMA, PCA, Morelet Continuous Wavelet Transform and Cross Correlations Dynamics), we investigated here the dynamics of ΔN₁₂₃-GB-CD2 alone and in interaction with sucrose substrate. Overall, our results provide the detailed picture at atomic level of the hierarchy of motions occurring along different timescales and how they are correlated, in agreement with experimental structural data. In particular, detailed analysis of the different structural domains revealed cooperative dynamic behaviors such as twisting, bending and wobbling through anti- and correlated motions, and also two structural hinge regions, of which one was unreported. Several highly flexible loops surrounding the catalytic pocket were also highlighted, suggesting a potential role in the acceptor promiscuity of ΔN123-GBD-CD2. Normal modes and essential dynamics underlined an interesting two-fold dynamic of the catalytic domain A, pivoting about an axis splitting the catalytic gorge in two parts. The comparison of the conformational free energy landscapes using principal component analysis of the enzyme in absence or in presence of sucrose, also revealed a more harmonic basin when sucrose is bound with a shift population of the bending mode, consistent with the substrate binding event.</p></div