GAPPED BLAST AND PSI-BLAST - A NEW-GENERATION OF PROTEIN DATABASE SEARCH PROGRAMS

The BLAST programs are widely used tools for searching protein and DNA databases for sequence similarities. For protein comparisons, a varie ty of definitional, algorithmic and statistical refinements described here permits the execution time of the BLAST programs to be decreased substantially while enhancing their sensitivity to weak similarities, A new criterion for triggering the extension of word hits, combined wi th a new heuristic for generating gapped alignments, yields a gapped B LAST program that runs at approximately three times the speed of the o riginal, In addition, a method is introduced for automatically combini ng statistically significant alignments produced by BLAST into a posit ion-specific score matrix, and searching the database using this matri x, The resulting Position-Specific Iterated BLAST (PSI-BLAST) program runs at approximately the same speed per iteration as gapped BLAST, bu t in many cases is much more sensitive to weak but biologically releva nt sequence similarities. PSI-BLAST is used to uncover several new and interesting members of the BRCT superfamily.