New avenues in protein function prediction.
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Algorithms↗
Biomedical subjects
Martin Jambon
Publications and source records attributed to Martin Jambon.
The SuMo server: 3D search for protein functional sites.
UNLABELLED: We provide the scientific community with a web server which gives access to SuMo, a bioinformatic system for finding similarities in arbitrary 3D structures or substructures of proteins. SuMo is based on a unique representation of macromolecules using selected triplets of chemical groups having their own geometry and symmetry, regardless of the restrictive notions of main chain and lateral chains of amino acids. The heuristic for extracting similar sites was used to drive two major large-scale approaches. First, searching for ligand binding sites onto a query structure has been made possible by comparing the structure against each of the ligand binding sites found in the Protein Data Bank (PDB). Second, the reciprocal process, i.e. searching for a given 3D site of interest among the structures of the PDB is also possible and helps detect cross-reacting targets in drug design projects. AVAILABILITY: The web server is freely accessible to academia through http://sumo-pbil.ibcp.fr and full support is available from MEDIT (http://www.medit.fr). CONTACT: mjambon@burnham.org.
Amino Acid Sequence↗
A new bioinformatic approach to detect common 3D sites in protein structures.
An innovative bioinformatic method has been designed and implemented to detect similar three-dimensional (3D) sites in proteins. This approach allows the comparison of protein structures or substructures and detects local spatial similarities: this method is completely independent from the amino acid sequence and from the backbone structure. In contrast to already existing tools, the basis for this method is a representation of the protein structure by a set of stereochemical groups that are defined independently from the notion of amino acid. An efficient heuristic for finding similarities that uses graphs of triangles of chemical groups to represent the protein structures has been developed. The implementation of this heuristic constitutes a software named SuMo (Surfing the Molecules), which allows the dynamic definition of chemical groups, the selection of sites in the proteins, and the management and screening of databases. To show the relevance of this approach, we focused on two extreme examples illustrating convergent and divergent evolution. In two unrelated serine proteases, SuMo detects one common site, which corresponds to the catalytic triad. In the legume lectins family composed of >100 structures that share similar sequences and folds but may have lost their ability to bind a carbohydrate molecule, SuMo discriminates between functional and non-functional lectins with a selectivity of 96%. The time needed for searching a given site in a protein structure is typically 0.1 s on a PIII 800MHz/Linux computer; thus, in further studies, SuMo will be used to screen the PDB.
Algorithms↗
Evidence for crucial electrostatic interactions between Bcl-2 homology domains BH3 and BH4 in the anti-apoptotic Nr-13 protein.
Nr-13 is an anti-apoptotic member of the Bcl-2 family previously shown to interact with Bax. The biological significance of this interaction was explored both in yeast and vertebrate cells and revealed that Nr-13 is able to counteract the pro-apoptotic activity of Bax. The Bax-interacting domain has been identified and corresponds to alpha-helices 5 and 6 in Nr-13. Site-directed mutagenesis has revealed that the N-terminal region of Nr-13 is essential for activity and corresponds to a genuine Bcl-2 homology domain (BH4). The modelling of Nr-13, based on its similarity with other Bcl-2 family proteins and energy minimization, suggests the possibility of electrostatic interactions between the two N-terminal-conserved domains BH4 and BH3. Disruption of these interactions severely affects Nr-13 anti-apoptotic activity. Together our results suggest that electrostatic interactions between BH4 and BH3 domains play a role in the control of activity of Nr-13 and a subset of Bcl-2 family members.
Amino Acid Sequence↗
Geno3D: automatic comparative molecular modelling of protein.
Geno3D (http://geno3d-pbil.ibcp.fr) is an automatic web server for protein molecular modelling. Starting with a query protein sequence, the server performs the homology modelling in six successive steps: (i) identify homologous proteins with known 3D structures by using PSI-BLAST; (ii) provide the user all potential templates through a very convenient user interface for target selection; (iii) perform the alignment of both query and subject sequences; (iv) extract geometrical restraints (dihedral angles and distances) for corresponding atoms between the query and the template; (v) perform the 3D construction of the protein by using a distance geometry approach and (vi) finally send the results by e-mail to the user.
Algorithms↗