MOTIVATION: ConSeq is a web server for the identification of biologically important residues in protein sequences. Functionally important residues that take part, e.g. in ligand binding and protein-protein interactions, are often evolutionarily conserved and are most likely to be solvent-accessible, whereas conserved residues within the protein core most probably have an important structural role in maintaining the protein's fold. Thus, estimated evolutionary rates, as well as relative solvent accessibility predictions, are assigned to each amino acid in the sequence; both are subsequently used to indicate residues that have potential structural or functional importance. AVAILABILITY: The ConSeq web server is available at http://conseq.bioinfo.tau.ac.il/ SUPPLEMENTARY INFORMATION: The ConSeq methodology, a description of its performance in a set of five well-documented proteins, a comparison to other methods, and the outcome of its application to a set of 111 proteins of unknown function, are presented at http://conseq.bioinfo.tau.ac.il/ under 'OVERVIEW', 'VALIDATION', 'COMPARISON' and 'PREDICTIONS', respectively.

Abstract Summary: We recently developed algorithmic tools for the identification of functionally important regions in proteins of known three dimensional structure by estimating the degree of conservation of the amino-acid sites among their close sequence homologues. Projecting the conservation grades onto the molecular surface of these proteins reveals patches of highly conserved (or occasionally highly variable) residues that are often of important biological function. We present a new web server, ConSurf, which automates these algorithmic tools. ConSurf may be used for high-throughput characterization of functional regions in proteins. Availability: The ConSurf web server is available at:http://consurf.tau.ac.il. Contact: [email protected]@[email protected]@[email protected]@[email protected] Supplementary Information: A set of examples is available at http://consurf.tau.ac.il under ‘GALLERY’. * To whom correspondence should be addressed.