Getting the most from PSI-BLAST.

Most biologists now conduct sequence searches as a matter of course. But how do we know that a relationship predicted by a homology search is a true, rather than false, hit with the same score? Many biologists design their own experiments with exquisite care yet still assume that results from programs with more than 20 adjustable parameters are 100% reliable. This article explains some of the key steps in getting the most from PSI-Blast, one of the most popular and powerful homology search programs currently available.

[1]  M. Sternberg,et al.  Benchmarking PSI-BLAST in genome annotation. , 1999, Journal of molecular biology.

[2]  W R Taylor,et al.  A model recognition approach to the prediction of all-helical membrane protein structure and topology. , 1994, Biochemistry.

[3]  R. Mott,et al.  Accurate formula for P-values of gapped local sequence and profile alignments. , 2000, Journal of molecular biology.

[4]  Thomas L. Madden,et al.  Improving the accuracy of PSI-BLAST protein database searches with composition-based statistics and other refinements. , 2001, Nucleic acids research.

[5]  P Bork,et al.  Positionally cloned human disease genes: patterns of evolutionary conservation and functional motifs. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[6]  John C. Wootton,et al.  Statistics of Local Complexity in Amino Acid Sequences and Sequence Databases , 1993, Comput. Chem..

[7]  A. Lupas,et al.  Predicting coiled coils from protein sequences , 1991, Science.

[8]  C A Orengo,et al.  Combining sensitive database searches with multiple intermediates to detect distant homologues. , 1999, Protein engineering.

[9]  Mitsuhiko Ikura,et al.  NMR structure of the histidine kinase domain of the E. coli osmosensor EnvZ , 1998, Nature.

[10]  D. Ohlendorf,et al.  The structure of the superantigen exfoliative toxin A suggests a novel regulation as a serine protease. , 1997, Biochemistry.

[11]  M. Brush CAST OF NEW PLAYERS: A PROFILE OF NEW PRECAST GELS FOR NUCLEIC ACID , 1999 .

[12]  D. Haussler,et al.  Sequence comparisons using multiple sequences detect three times as many remote homologues as pairwise methods. , 1998, Journal of molecular biology.

[13]  S F Altschul,et al.  Iterated profile searches with PSI-BLAST--a tool for discovery in protein databases. , 1998, Trends in biochemical sciences.

[14]  P Bork,et al.  Homology-based fold predictions for Mycoplasma genitalium proteins. , 1998, Journal of molecular biology.

[15]  M S Waterman,et al.  Identification of common molecular subsequences. , 1981, Journal of molecular biology.

[16]  Richard Mott Local sequence alignments with monotonic gap penalties , 1999, Bioinform..