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

FOSS EKV2.6 Verilog-A Compact MOSFET Model

The EKV2.6 MOSFET compact model has had a considerable impact on the academic and industrial community of analog integrated circuit design, since its inception in 1996. The model is available as a free open-source software (FOSS) tool coded in Verilog-A. The present paper provides a short review of foundations of the model and shows its capabilities via characterization and modeling based on a test chip in 180 nm CMOS fabricated via Europractice

Intrinsic flexibility of B-DNA: the experimental TRX scale

B-DNA flexibility, crucial for DNA–protein recognition, is sequence dependent. Free DNA in solution would in principle be the best reference state to uncover the relation between base sequences and their intrinsic flexibility; however, this has long been hampered by a lack of suitable experimental data. We investigated this relationship by compiling and analyzing a large dataset of NMR 31P chemical shifts in solution. These measurements reflect the BI ↔ BII equilibrium in DNA, intimately correlated to helicoidal descriptors of the curvature, winding and groove dimensions. Comparing the ten complementary DNA dinucleotide steps indicates that some steps are much more flexible than others. This malleability is primarily controlled at the dinucleotide level, modulated by the tetranucleotide environment. Our analyses provide an experimental scale called TRX that quantifies the intrinsic flexibility of the ten dinucleotide steps in terms of Twist, Roll, and X-disp (base pair displacement). Applying the TRX scale to DNA sequences optimized for nucleosome formation reveals a 10 base-pair periodic alternation of stiff and flexible regions. Thus, DNA flexibility captured by the TRX scale is relevant to nucleosome formation, suggesting that this scale may be of general interest to better understand protein-DNA recognition

Understanding the Sequence-Dependence of DNA Groove Dimensions: Implications for DNA Interactions

BACKGROUND: The B-DNA major and minor groove dimensions are crucial for DNA-protein interactions. It has long been thought that the groove dimensions depend on the DNA sequence, however this relationship has remained elusive. Here, our aim is to elucidate how the DNA sequence intrinsically shapes the grooves. METHODOLOGY/PRINCIPAL FINDINGS: The present study is based on the analysis of datasets of free and protein-bound DNA crystal structures, and from a compilation of NMR (31)P chemical shifts measured on free DNA in solution on a broad range of representative sequences. The (31)P chemical shifts can be interpreted in terms of the BI↔BII backbone conformations and dynamics. The grooves width and depth of free and protein-bound DNA are found to be clearly related to the BI/BII backbone conformational states. The DNA propensity to undergo BI↔BII backbone transitions is highly sequence-dependent and can be quantified at the dinucleotide level. This dual relationship, between DNA sequence and backbone behavior on one hand, and backbone behavior and groove dimensions on the other hand, allows to decipher the link between DNA sequence and groove dimensions. It also firmly establishes that proteins take advantage of the intrinsic DNA groove properties. CONCLUSIONS/SIGNIFICANCE: The study provides a general framework explaining how the DNA sequence shapes the groove dimensions in free and protein-bound DNA, with far-reaching implications for DNA-protein indirect readout in both specific and non specific interactions

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

Displacive transformations and quasicrystalline symmetries

The property, for quasiperiodic structures built by the cut and project or any equivalent method, to be related to a periodic lattice by a bounded deformation is a strong restriction on the window defining the strip, or on the atomic surface. We give a sufficient condition (which is also necessary in one dimension) for the existence of such a bounded modulation to a lattice which requires that the window tiles the orthogonal space. Using a special procedure we extend our proof to more general, albeit still non generic, situations including tilings of the Penrose type.La propriété, pour une structure quasi-périodique obtenue par coupe et projection ou toute autre méthode équivalente, d'être liée à un réseau moyen par une déformation bornée est une forte restriction sur la fenêtre définissant la bande, ou sur la surface atomique. Nous donnons une condition suffisante (nécessaire à une dimension) pour l'existence d'une telle modulation vers un réseau, qui stipule que la fenêtre pave l'espace orthogonal. Grâce à une construction spéciale nous étendons notre preuve à des situations plus générales, bien que non génériques, incluant les pavages du type Penrose

From 2D Hyperbolic Forests to 3D Euclidean Entangled Thickets

A method is developed to construct and analyse a wide class of graphs embedded in Euclidean 3D space, including multiply-connected and entangled examples. The graphs are derived via embeddings of infinite families of trees (forests) in the hyperbolic plane, and subsequent folding into triply periodic minimal surfaces, including the P, D, gyroid and H surfaces. Some of these graphs are natural generalisations of bicontinuous topologies to bi-, tri-, quadra-and octa-continuous forms. Interwoven layer graphs and periodic sets of finite clusters also emerge from the algorithm. Many of the graphs are chiral. The generated graphs are compared with some organo-metallic molecular crystals with multiple frameworks and molecular mesophases found in copolymer melts

Modelling relaxation following T1 transformations of foams incorporating surfactant mass transfer by the Marangoni effect

The dynamics following T1 transformation of foams, during which certain foam films shrink and others grow, was modelled. Variation in surface tension due both to change in surfactant concentration and viscous drag was taken into account. Surfactant transfer was also taken into account, which was assumed to take place between connected films and to be caused by the Marangoni effect. Two models were considered in the first instance, one treating the two sides of shrinking films to be identical and another treating them to be different. Numerical results show plausible behaviours in certain parameter regimes, however with several potential issues. In particular, in one model, singularity was observed above a certain value of the surfactant mass transport coefficient, while such an event was avoided in the other model, as large tension differences between adjacent films are then suppressed. Analysing the results and comparing the models, with a view to applying them to a hexagonal honeycomb foam (rather than just to an isolated set of films), led to a possibility of further improvement; namely incorporating an inter-system surfactant transfer and variation in both surface tension and surfactant concentration along individual films, on top of the mechanisms already considered. Inter-system surfactant transfer was readily incorporated into a third model, which again displayed plausible behaviour

Tricontinuous mesophases of balanced three-arm 'star polyphiles'

We construct simple models to compare ordered tricontinuous patterns that are topologically consistent with the constraints imposed by three-arm star polyphile self-assembly, analogous to steric packing and elastic bending models used to analyse bicontinuous mesophases in amphiphilic assemblies. We find a number of competing low-energy ordered structures, composed of threading of three identical labyrinths, with three-fold infinite branch lines, that are likely to be of comparable energy for polyphile shapes with moderately splayed arms. These patterns are triply-periodic analogues of the hexagonal honeycomb, which is most favoured for unsplayed three-arm polyphile architectures