Automated assembly of protein blocks for database searching

A system is described for finding and assembling the most highly conserved regions of related proteins for database searching. First, an automated version of Smith's algorithm for finding motifs is used for sensitive detection of multiple local alignments. Next, the local alignments are converted to blocks and the best set of non-overlapping blocks is determined. When the automated system was applied successively to all 437 groups of related proteins in the PROSITE catalog, 1764 blocks resulted; these could be used for very sensitive searches of sequence databases. Each block was calibrated by searching the SWISS-PROT database to obtain a measure of the chance distribution of matches, and the calibrated blocks were concatenated into a database that could itself be searched. Examples are provided in which distant relationships are detected either using a set of blocks to search a sequence database or using sequences to search the database of blocks. The practical use of the blocks database is demonstrated by detecting previously unknown relationships between oxidoreductases and by evaluating a proposed relationship between HIV Vif protein and thiol proteases.