A convolutional-like approach to p-adic codes

AbstractIn this paper, we will see that codes defined over p-adic fields can be used in the same way as convolutional codes. We will prove some theoretical results concerning their encoders and show that, in practice, they can be encoded and decoded efficiently

DG-AMMOS: A New tool to generate 3D conformation of small molecules using Distance Geometry and Automated Molecular Mechanics Optimization for in silico Screening

<p>Abstract</p> <p>Background</p> <p>Discovery of new bioactive molecules that could enter drug discovery programs or that could serve as chemical probes is a very complex and costly endeavor. Structure-based and ligand-based <it>in silico </it>screening approaches are nowadays extensively used to complement experimental screening approaches in order to increase the effectiveness of the process and facilitating the screening of thousands or millions of small molecules against a biomolecular target. Both <it>in silico </it>screening methods require as input a suitable chemical compound collection and most often the 3D structure of the small molecules has to be generated since compounds are usually delivered in 1D SMILES, CANSMILES or in 2D SDF formats.</p> <p>Results</p> <p>Here, we describe the new open source program DG-AMMOS which allows the generation of the 3D conformation of small molecules using Distance Geometry and their energy minimization via Automated Molecular Mechanics Optimization. The program is validated on the Astex dataset, the ChemBridge Diversity database and on a number of small molecules with known crystal structures extracted from the Cambridge Structural Database. A comparison with the free program Balloon and the well-known commercial program Omega generating the 3D of small molecules is carried out. The results show that the new free program DG-AMMOS is a very efficient 3D structure generator engine.</p> <p>Conclusion</p> <p>DG-AMMOS provides fast, automated and reliable access to the generation of 3D conformation of small molecules and facilitates the preparation of a compound collection prior to high-throughput virtual screening computations. The validation of DG-AMMOS on several different datasets proves that generated structures are generally of equal quality or sometimes better than structures obtained by other tested methods.</p

Propriétés mécaniques, structure interne et mécanismes de transfert de l'oxygène dans le liège

During the post bottling aging, premature oxidation reactions could occur and the oxygen barrier properties of the stopper are often pointed out. Nowadays, the internal structure of this material or the effect of hydration on its mechanical properties are still undetermined. Moreover, regarding the barrier properties, the limiting step of the oxygen transfer was not yet fully understood as well as the effect of compression or the role of the glass/cork interface in a bottleneck. The study of the internal structure of cork stopper allowed us to visualize the macroporosity of the material and conclude that there is no interconnectivity between lenticels, for the two qualities studied. The effect of hydration on the mechanical properties of cork was also investigated. The results shown that the rigidity of the material was not significantly affected for relative humidity < 50 %. Above this hydration level, the Young’s moduli decrease due to clusters formation of water molecules. Comparing the natural cork behavior to other stoppers, an effect of the particle size and the ratio cork/additives used in these stoppers was also highlighted. Regarding the transport mechanism of gas through cork, the limiting step was clearly determined: it’s the diffusion through the cell wall according to a Fickian mechanism. The compression of the stopper does not have a significant impact on the effective diffusion coefficient of oxygen. However, the role of the glass/cork interface is really important and seems to govern the gas transfer from the surrounding atmosphere into the bottle.Lors de la conservation des vins en bouteilles, des réactions d’oxydation prématurées peuvent se produire et les propriétés barrières à l’oxygène de l’obturateur en liège sont souvent mises en cause. À l’heure actuelle, aucune étude n’a permis de déterminer la structure interne du liège ou l’effet de l’hydratation sur ses propriétés mécaniques. Quant aux propriétés barrières à l’oxygène, l’étape limitante au transfert reste indéterminée ainsi que l’effet de la compression et le rôle de l’interface verre/liège. L’étude de la structure interne du liège par imagerie a permis de visualiser la macroporosité du matériau et de conclure que pour les qualités de liège étudiées, les lenticelles ne sont pas interconnectées. La caractérisation des propriétés mécaniques du liège a montré que le module de Young n’était pas affecté pour une humidité relative < 50 %. En milieu plus humide, ce dernier diminue à cause de la formation de clusters de molécules d’eau entre les chaines de polymères constituants les parois cellulaires. En comparant le comportement du liège brut avec celui d’autres obturateurs, un effet de la taille des particules de liège et du ratio liège/additifs utilisés dans ces obturateurs, a également été mis en évidence. Au regard du mécanisme de transfert de gaz, les mécanismes en jeu et en particulier l’étape limitante ont été clairement déterminés : il s’agit de la diffusion au travers des parois cellulaires selon la loi de Fick. L’effet de la compression du bouchon ne modifie pas significativement le transfert d’oxygène tandis que le rôle de l’interface verre/liège semble gouverner les transferts de gaz de l’extérieur vers l’intérieur de la bouteille

MS-DOCK: Accurate multiple conformation generator and rigid docking protocol for multi-step virtual ligand screening

<p>Abstract</p> <p>Background</p> <p>The number of protein targets with a known or predicted tri-dimensional structure and of drug-like chemical compounds is growing rapidly and so is the need for new therapeutic compounds or chemical probes. Performing flexible structure-based virtual screening computations on thousands of targets with millions of molecules is intractable to most laboratories nor indeed desirable. Since shape complementarity is of primary importance for most protein-ligand interactions, we have developed a tool/protocol based on rigid-body docking to select compounds that fit well into binding sites.</p> <p>Results</p> <p>Here we present an efficient multiple conformation rigid-body docking approach, MS-DOCK, which is based on the program DOCK. This approach can be used as the first step of a multi-stage docking/scoring protocol. First, we developed and validated the Multiconf-DOCK tool that generates several conformers per input ligand. Then, each generated conformer (bioactives and 37970 decoys) was docked rigidly using DOCK6 with our optimized protocol into seven different receptor-binding sites. MS-DOCK was able to significantly reduce the size of the initial input library for all seven targets, thereby facilitating subsequent more CPU demanding flexible docking procedures.</p> <p>Conclusion</p> <p>MS-DOCK can be easily used for the generation of multi-conformer libraries and for shape-based filtering within a multi-step structure-based screening protocol in order to shorten computation times.</p