Non Ribosomal Peptides : A monomeric puzzle

National audienceNonribosomal peptides (NRPs) are increasingly studied because they harbor activities which can be exploited in various domains. They are often denoted as graphs illustrating their chemical structure, where the atoms are represented by nodes and the chemical bonds by arcs. Another possible representation is the monomeric structure. This structure, inspired by the biosynthetic pathway of these peptides, is effectuated by large enzymatic complexes which assemble together smaller compounds called monomers. Consequently, the nonribosomal peptides are composed of a great variety of monomers (more than 500 are known) including amino acids, lipids and carbohydrates. Likewise, nonpetidic bonds are formed between multiple monomers, producing peptides with cycles and/or branches. Thus, the monomeric structure is a graph formed by the monomers present in the peptide and their interlinking chemical bonds. Until now, there did not exist a tool allowing for the conversion between the atomic and monomeric structures. This article presents a novel algorithm capable of localising the monomers from a reference list in the chemical structures of peptides extracted from the Norine database. The algorithm is based on a heuristic that utilizes chemical information of NRPs. The preliminary results are encouraging, and should lead to further studies.Les peptides non-ribosomiques (NRP) sont des molécules de plus en plus étudiées car elles présentent des activités ayant des applications principalement dans le domaine pharmaceutique. Elles sont souvent décrites par leur structure chimique, c'est-a-dire un graphe dont les noeuds sont des atomes et les arêtes les liaisons chimiques. Une autre représentation possible est la structure monomérique. Cette structure, inspirée de la voie de synthèse de ces peptides, est réalisé par de gros complexes enzymatiques qui assemblent les briques de base, appelées monomères. Ainsi, les peptides non-ribosomiques sont composés d'une grande variété de monomères (plus de 500 recensés jusqu'à présent) tels que des acides aminés, mais aussi des lipides ou des sucres. De plus, des liaisons non-peptidiques peuvent être formées entre certains monomères, ce qui produit des peptides contenant des cycles et/ou des branchements. La structure monomérique est donc le graphe formé par les monomères présents dans le peptide et les liaisons qui les relient. A l'heure actuelle, il n'existe pas d'outil permettant de convertir la structure chimique d'un peptide non-ribosomique en sa structure monomérique. Cet article présente un algorithme capable de localiser les monomères d'une liste de référence dans les structures chimiques des peptides de la base de données Norine. Il est basé sur une heuristique gloutonne qui utilise des connaissances sur la chimie des NRP. Les résultats préliminaires sont satisfaisants et devraient conduire à de nouvelles études

Structural pattern matching of nonribosomal peptides

<p>Abstract</p> <p>Background</p> <p>Nonribosomal peptides (NRPs), bioactive secondary metabolites produced by many microorganisms, show a broad range of important biological activities (e.g. antibiotics, immunosuppressants, antitumor agents). NRPs are mainly composed of amino acids but their primary structure is not always linear and can contain cycles or branchings. Furthermore, there are several hundred different monomers that can be incorporated into NRPs. The N<smcaps>ORINE</smcaps> database, the first resource entirely dedicated to NRPs, currently stores more than 700 NRPs annotated with their monomeric peptide structure encoded by undirected labeled graphs. This opens a way to a systematic analysis of structural patterns occurring in NRPs. Such studies can investigate the functional role of some monomeric chains, or analyse NRPs that have been computationally predicted from the synthetase protein sequence. A basic operation in such analyses is the search for a given structural pattern in the database.</p> <p>Results</p> <p>We developed an efficient method that allows for a quick search for a structural pattern in the N<smcaps>ORINE</smcaps> database. The method identifies all peptides containing a pattern substructure of a given size. This amounts to solving a variant of the maximum common subgraph problem on pattern and peptide graphs, which is done by computing cliques in an appropriate compatibility graph.</p> <p>Conclusion</p> <p>The method has been incorporated into the N<smcaps>ORINE</smcaps> database, available at <url>http://bioinfo.lifl.fr/norine</url>. Less than one second is needed to search for a pattern in the entire database.</p

L codent, L créent: créations numériques artistiques pour démystifier l'informatique... au féminin! (descriptif d’atelier)

International audienceLe secteur informatique connaît un déséquilibre importante de genre malgré une forte implication de femmesau début du développement de l’informatique à la fin des années 1950. Ce phénomène s’est accéléré dans lesannées 1980 et depuis la situation continue à se détériorer. Afin de lutter contre cette tendance, le groupe detravail « Informatique au féminin » et le collectif "ch’ticode" de l’Université de Lille - Sciences & Technologies ontexpérimenté une action de médiation en informatique à destination de collégiennes encadrées par des étudiantesinformaticiennes. L’atelier permettra aux participants de découvrir les activités proposées et l’organisation del’activité, ainsi qu’un retour d’expérience sur cette première saison qui est renouvelée cette année et sera étendueà un lycée

NRPS toolbox for the discovery of new nonribosomal peptides and synthetases

National audienceNonribosomal peptide synthetases are huge multi-enzymatic complexes synthesizing peptides, but not through the classical process of transcription and then translation. The synthetases are organised in modules, each one integrating an amino acid in the final peptide. The modules are divided in domains providing specialized activities. So, those enzymes are as diverse as their products. We present our toolbox designed to annotate them accurately and promising results obtained on some Burkholderia, Bacillus and Pseudomonas genomes

NORINE: a database of nonribosomal peptides

Norine is the first database entirely dedicated to nonribosomal peptides (NRPs). In bacteria and fungi, in addition to the traditional ribosomal proteic biosynthesis, an alternative ribosome-independent pathway called NRP synthesis allows peptide production. It is performed by huge protein complexes called nonribosomal peptide synthetases (NRPSs). The molecules synthesized by NRPS contain a high proportion of nonproteogenic amino acids. The primary structure of these peptides is not always linear but often more complex and may contain cycles and branchings. In recent years, NRPs attracted a lot of attention because of their biological activities and pharmacological properties (antibiotic, immunosuppressor, antitumor, etc.). However, few computational resources and tools dedicated to those peptides have been available so far. Norine is focused on NRPs and contains more than 700 entries. The database is freely accessible at http://bioinfo.lifl.fr/norine/. It provides a complete computational tool for systematic study of NRPs in numerous species, and as such, should permit to obtain a better knowledge of these metabolic products and underlying biological mechanisms, and ultimately to contribute to the redesigning of natural products in order to obtain new bioactive compounds for drug discovery

How to make teenage girls love coding ?

International audienceToo few women work in IT. It's a pity as it deprives women of exciting jobs and computing of women viewpoint. So, members of Lille University decided to fight prejudices by making female computer science students teach coding to teenage girls, using Python and the visual arts language Processing

Comparing sequences without using alignments: application to HIV/SIV subtyping

BACKGROUND: In general, the construction of trees is based on sequence alignments. This procedure, however, leads to loss of informationwhen parts of sequence alignments (for instance ambiguous regions) are deleted before tree building. To overcome this difficulty, one of us previously introduced a new and rapid algorithm that calculates dissimilarity matrices between sequences without preliminary alignment. RESULTS: In this paper, HIV (Human Immunodeficiency Virus) and SIV (Simian Immunodeficiency Virus) sequence data are used to evaluate this method. The program produces tree topologies that are identical to those obtained by a combination of standard methods detailed in the HIV Sequence Compendium. Manual alignment editing is not necessary at any stage. Furthermore, only one user-specified parameter is needed for constructing trees. CONCLUSION: The extensive tests on HIV/SIV subtyping showed that the virus classifications produced by our method are in good agreement with our best taxonomic knowledge, even in non-coding LTR (Long Terminal Repeat) regions that are not tractable by regular alignment methods due to frequent duplications/insertions/deletions. Our method, however, is not limited to the HIV/SIV subtyping. It provides an alternative tree construction without a time-consuming aligning procedure

Non Ribosomal Peptides : A monomeric puzzle

National audienceNonribosomal peptides (NRPs) are increasingly studied because they harbor activities which can be exploited in various domains. They are often denoted as graphs illustrating their chemical structure, where the atoms are represented by nodes and the chemical bonds by arcs. Another possible representation is the monomeric structure. This structure, inspired by the biosynthetic pathway of these peptides, is effectuated by large enzymatic complexes which assemble together smaller compounds called monomers. Consequently, the nonribosomal peptides are composed of a great variety of monomers (more than 500 are known) including amino acids, lipids and carbohydrates. Likewise, nonpetidic bonds are formed between multiple monomers, producing peptides with cycles and/or branches. Thus, the monomeric structure is a graph formed by the monomers present in the peptide and their interlinking chemical bonds. Until now, there did not exist a tool allowing for the conversion between the atomic and monomeric structures. This article presents a novel algorithm capable of localising the monomers from a reference list in the chemical structures of peptides extracted from the Norine database. The algorithm is based on a heuristic that utilizes chemical information of NRPs. The preliminary results are encouraging, and should lead to further studies.Les peptides non-ribosomiques (NRP) sont des molécules de plus en plus étudiées car elles présentent des activités ayant des applications principalement dans le domaine pharmaceutique. Elles sont souvent décrites par leur structure chimique, c'est-a-dire un graphe dont les noeuds sont des atomes et les arêtes les liaisons chimiques. Une autre représentation possible est la structure monomérique. Cette structure, inspirée de la voie de synthèse de ces peptides, est réalisé par de gros complexes enzymatiques qui assemblent les briques de base, appelées monomères. Ainsi, les peptides non-ribosomiques sont composés d'une grande variété de monomères (plus de 500 recensés jusqu'à présent) tels que des acides aminés, mais aussi des lipides ou des sucres. De plus, des liaisons non-peptidiques peuvent être formées entre certains monomères, ce qui produit des peptides contenant des cycles et/ou des branchements. La structure monomérique est donc le graphe formé par les monomères présents dans le peptide et les liaisons qui les relient. A l'heure actuelle, il n'existe pas d'outil permettant de convertir la structure chimique d'un peptide non-ribosomique en sa structure monomérique. Cet article présente un algorithme capable de localiser les monomères d'une liste de référence dans les structures chimiques des peptides de la base de données Norine. Il est basé sur une heuristique gloutonne qui utilise des connaissances sur la chimie des NRP. Les résultats préliminaires sont satisfaisants et devraient conduire à de nouvelles études

Data updates on Norine, the reference Non-Ribosomal Peptide knowledge base

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