IMPALA: matching a protein sequence against a collection of PSI-BLAST-constructed position-specific score matrices

Motivation: Many studies have shown that database searches using position-s pecific score matrices (PSSMs) or profiles as queries are more effective at identifying distant protein relationships than are searches that use simpl e sequences as queries. One popular program for constructing a PSSM and com paring it with a database of sequences is Position-Specific Iterated BLAST (PSI-BLAST). Results: This paper describes a new software package, IMPALA, designed for the complementary procedure of comparing a single query sequence with a dat abase of PSI-BLAST-generated PSSMs. We illustrate the use of IMPALA to sear ch a database of PSSMs for protein folds, and one for protein domains invol ved in signal transduction. IMPALA's sensitivity to distant biological rela tionships is very similar to that of PSI-BLAST. However, IMPALA employs a m ore refined analysis of statistical significance and, unlike PSI-BLAST, gua rantees the output of the optimal local alignment by using the rigorous Smi th-Waterman algorithm. Also, it is considerably faster when run with a larg e database of PSSMs than is BLAST or PSI-BLAST when run against the complet e non-redundant protein database.