Frog: a FRee Online druG 3D conformation generator

In silico screening methods based on the 3D structures of the ligands or of the proteins have become an essential tool to facilitate the drug discovery process. To achieve such process, the 3D structures of the small chemical compounds have to be generated. In addition, for ligand-based screening computations or hierarchical structure-based screening projects involving a rigid-body docking step, it is necessary to generate multi-conformer 3D models for each input ligand to increase the efficiency of the search. However, most academic or commercial compound collections are delivered in 1D SMILES (simplified molecular input line entry system) format or in 2D SDF (structure data file), highlighting the need for free 1D/2D to 3D structure generators. Frog is an on-line service aimed at generating 3D conformations for drug-like compounds starting from their 1D or 2D descriptions. Given the atomic constitution of the molecules and connectivity information, Frog can identify the different unambiguous isomers corresponding to each compound, and generate single or multiple low-to-medium energy 3D conformations, using an assembly process that does not presently consider ring flexibility. Tests show that Frog is able to generate bioactive conformations close to those observed in crystallographic complexes. Frog can be accessed at http://bioserv.rpbs.jussieu.fr/Frog.html

Mutations in SPG11, encoding spatacsin, are a major cause of spastic paraplegia with thin corpus callosum.

Autosomal recessive hereditary spastic paraplegia (ARHSP) with thin corpus callosum (TCC) is a common and clinically distinct form of familial spastic paraplegia that is linked to the SPG11 locus on chromosome 15 in most affected families. We analyzed 12 ARHSP-TCC families, refined the SPG11 candidate interval and identified ten mutations in a previously unidentified gene expressed ubiquitously in the nervous system but most prominently in the cerebellum, cerebral cortex, hippocampus and pineal gland. The mutations were either nonsense or insertions and deletions leading to a frameshift, suggesting a loss-of-function mechanism. The identification of the function of the gene will provide insight into the mechanisms leading to the degeneration of the corticospinal tract and other brain structures in this frequent form of ARHSP

RPBS: a web resource for structural bioinformatics

RPBS (Ressource Parisienne en Bioinformatique Structurale) is a resource dedicated primarily to structural bioinformatics. It is the result of a joint effort by several teams to set up an interface that offers original and powerful methods in the field. As an illustration, we focus here on three such methods uniquely available at RPBS: AUTOMAT for sequence databank scanning, YAKUSA for structure databank scanning and WLOOP for homology loop modelling. The RPBS server can be accessed at and the specific services at

HYBRIDIZATION EFFECTS IN SOLIDS STUDIED BY COMPTON SCATTERING

Nous présentons une série de mesures de profils Compton sur des cristaux de LiH et de LiC6. La comparaison avec les profils calculés permet de tester la qualité des fonctions d'onde du système, et par là de vérifier si la base de fonctions d'onde utilisées pour créer les orbitales prend en compte toutes les hybridations éventuelles.We present a serie of measurements of Compton profiles on LiH and LiC6 crystals.The comparison with calculated profiles is a test of the quality of the wave function of the system, and it allows to check if the basis set used to develop the wave function takes care of all eventual hybridizations

ELECTRON CORRELATION IN METALS EVIDENCED BY COMPTON SCATTERING

La différence entre profils Compton théorique - pseudopotentiel- et expérimental permet d'évaluer l'importance de la corrélation électronique dans les métaux. Pour le béryllium elle est quasi indépendante de la direction étudiée, alors que pour un composé lamellaire comme le graphite, elle est anisotrope. Dans le premier cas, un traitement de corrélations électroniques pour un gaz d'électrons supposé homogène, réduit de moitié la différence. Cette méthode ne peut s'appliquer au graphite pour améliorer le calcul mono électronique et il est nécessaire d'utiliser des fonctions d'onde multiélectroniques.The difference between theoretical -pseudopotential- and experimental Compton profiles allows to estimate the electron correlations in metals. For beryllium it is almost directionally independent, while for a lamellar compound such as graphite, also of hexagonal symmetry, the difference is anisotropic. In the first case the correlation effects evaluated for a homogenous electron gas, reduced the difference almost by a factor 2. This method cannot be used to improve the one-electron calculation in graphite and more advanced theories using multi electron wave functions are required

Molecular characterization of the major membrane skeletal protein in the ciliate Tetrahymena pyriformis suggests n-plication of an early evolutionary intermediate filament protein subdomain.

International audienceEpiplasmin C is the major protein component of the membrane skeleton in the ciliate Tetrahymena pyriformis. Cloning and analysis of the gene encoding epiplasmin C showed this protein to be a previously unrecognized protein. In particular, epiplasmin C was shown to lack the canonical features of already known epiplasmic proteins in ciliates and flagellates. By means of hydrophobic cluster analysis (HCA), it has been shown that epiplasmin C is constituted of a repeat of 25 domains of 40 residues each. These domains are related and can be grouped in two families called types I and types II. Connections between types I and types II present rules that can be evidenced in the sequence itself, thus enforcing the validity of the splitting of the domains. Using these repeated domains as queries, significant structural similarities were demonstrated with an extra six heptads shared by nuclear lamins and invertebrate cytoplasmic intermediate filament proteins and deleted in the cytoplasmic intermediate filament protein lineage at the protostome-deuterostome branching in the eukaryotic phylogenetic tree