Biomedical subjects

Jean-Christophe Gelly

Publications and source records attributed to Jean-Christophe Gelly.

4 recordsLinked to original sources

PubMed2005

'Protein Peeling': an approach for splitting a 3D protein structure into compact fragments.

MOTIVATION: The object of this study is to propose a new method to identify small compact units that compose protein three-dimensional structures. These fragments, called 'protein units (PU)', are a new level of description to well understand and analyze the organization of protein structures. The method only works from the contact probability matrix, i.e. the inter Calpha-distances translated into probabilities. It uses the principle of conventional hierarchical clustering, leading to a series of nested partitions of the 3D structure. Every step aims at dividing optimally a unit into 2 or 3 subunits according to a criterion called 'partition index' assessing the structural independence of the subunits newly defined. Moreover, an entropy-derived squared correlation R is used for assessing globally the protein structure dissection. The method is compared to other splitting algorithms and shows relevant performance. AVAILABILITY: An Internet server with dedicated tools is available at http://www.ebgm.jussieu.fr/~gelly/

Algorithms↗

PubMed2005

EvDTree: structure-dependent substitution profiles based on decision tree classification of 3D environments.

BACKGROUND: Structure-dependent substitution matrices increase the accuracy of sequence alignments when the 3D structure of one sequence is known, and are successful e.g. in fold recognition. We propose a new automated method, EvDTree, based on a decision tree algorithm, for automatic derivation of amino acid substitution probabilities from a set of sequence-structure alignments. The main advantage over other approaches is an unbiased automatic selection of the most informative structural descriptors and associated values or thresholds. This feature allows automatic derivation of structure-dependent substitution scores for any specific set of structures, without the need to empirically determine best descriptors and parameters. RESULTS: Decision trees for residue substitutions were constructed for each residue type from sequence-structure alignments extracted from the HOMSTRAD database. For each tree cluster, environment-dependent substitution profiles were derived. The resulting structure-dependent substitution scores were assessed using a criterion based on the mean ranking of observed substitution among all possible substitutions and in sequence-structure alignments. The automatically built EvDTree substitution scores provide significantly better results than conventional matrices and similar or slightly better results than other structure-dependent matrices. EvDTree has been applied to small disulfide-rich proteins as a test case to automatically derive specific substitutions scores providing better results than non-specific substitution scores. Analyses of the decision tree classifications provide useful information on the relative importance of different structural descriptors. CONCLUSIONS: We propose a fully automatic method for the classification of structural environments and inference of structure-dependent substitution profiles. We show that this approach is more accurate than existing methods for various applications. The easy adaptation of EvDTree to any specific data set opens the way for class-specific structure-dependent substitution scores which can be used in threading-based remote homology searches.

Alanine↗

PubMed2004

The KNOTTIN website and database: a new information system dedicated to the knottin scaffold.

The KNOTTIN website and database organize information about knottins or inhibitor cystine knots, small disulfide-rich proteins with a knotted topology. Thanks to their small size and high stability, knottins provide appealing scaffolds for protein engineering and drug design. Static pages present the main historical and recent results about knottin discoveries, sequences, structures, folding, functions, applications and bibliography. Database searches provide dynamically generated tabular reports or sequence alignments for knottin three-dimensional structures or sequences. BLAST/HMM searches are also available. A simple nomenclature, based on loop lengths between cysteines, is proposed and is complemented by a uniform numbering scheme. This standardization is applied to all knottin structures in the database, facilitating comparisons. Renumbered and structurally fitted knottin PDB files are available for download. The standardized numbering is used for automatic drawing of two-dimensional Colliers de Perles. The KNOTTIN website and database are available at http://knottin.cbs.cnrs.fr and http://knottin.com.

Amino Acid Motifs↗

PubMed2004

Squash inhibitors: from structural motifs to macrocyclic knottins.

In this article, we will first introduce the squash inhibitor, a well established family of highly potent canonical serine proteinase inhibitors isolated from Cucurbitaceae. The squash inhibitors were among the first discovered proteins with the typical knottin fold shared by numerous peptides extracted from plants, animals and fungi. Knottins contain three knotted disulfide bridges, two of them arranged as a Cystine-Stabilized Beta-sheet motif. In contrast to cyclotides for which no natural linear homolog is known, most squash inhibitors are linear. However, Momordica cochinchinensis Trypsin Inhibitor-I and (MCoTI-I and -II), 34-residue squash inhibitors isolated from seeds of a common Cucurbitaceae from Vietnam, were recently shown to be macrocyclic. In these circular squash inhibitors, a short peptide linker connects residues that correspond to the N- and C-termini in homologous linear squash inhibitors. In this review we present the isolation, characterization, chemical synthesis, and activity of these macrocyclic knottins. The solution structure of MCoTI-II will be compared with topologically similar cyclotides, homologous linear squash inhibitors and other knottins, and potential applications of such scaffolds will be discussed.

Amino Acid Sequence↗