Home > Archives > Fabian Glaser   Fabian Glaser Department of Biochemistry, George S. Wise Faculty of Life Sciences Tel Aviv University, Israel http://consurf.tau.ac.il A Server for the Identification of Functional Regions in Proteins by Surface-Mapping of Phylogenetic Information We have recently developed algorithmic tools for the identification of functionally important regions in a protein with a known three-dimensional (3D) structure by estimating the degree of conservation of the amino acid sites within its close sequence homologues. The basic premise of these algorithms is that the degree of conservation at each amino acid site is similar to the inverse of the site's rate of evolution; slowly evolving sites are evolutionarily conserved, while rapidly evolving sites are variable. Projecting the residue conservation grades onto the 3D structure of the protein usually reveals surface patches of highly conserved and occasionally highly variable residues that often have known or suspected biological functions[EM1] , or are predictive of such functions. Very recently we reported the development of a web server, ConSurf, which automates these algorithmic tools and enables easy, high throughput studies of proteins with known 3D-structure,. ConSurf is available to the scientific community at http://consurf.tau.ac.il (Glaser et al., Bioinformatics, in press). With a protein structure in PDB format, the server carries out a PSI-BLAST search for close sequence homologues of the selected polypeptide chain (subunit), subsequently aligning them using CLUSTAL W. Alternatively, the user can provide a previously-made multiple sequence alignment (MSA). In any event, the server builds a phylogenetic tree consistent with the MSA and estimates the conservation grades of each amino acid site, taking into account the evolutionary relations between the homologues. The protein can be finally visualized on-line using the powerful Protein Explorer engine with the conservation grades color-coded onto its surface. We are developing ConSurf further. For example, in the current implementation, the identification of the patches of conserved residues and the definition of their boundaries is subjective. We will introduce an automatic methodology to define the size and limits of each conserved cluster. We will also introduce an automatic methodology for analyzingmulti-domain proteins one domain at a time.
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