The PSI-BLAST algorithm has been acknowledged as
one of the most powerful tools for detecting remote evolutionary
relationships by sequence considerations only. This has
been demonstrated by its ability to recognize remote structural
homologues and by the greatest coverage it enables in annotation
of a complete genome. Although recognizing the correct
fold of a sequence is of major importance, the accuracy
of the alignment is crucial for the success of modeling
one sequence by the structure of its remote homologue.
Here we assess the accuracy of PSI-BLAST alignments on
a stringent database of 123 structurally similar, sequence-dissimilar
pairs of proteins, by comparing them to the alignments
defined on a structural basis. Each protein sequence is
compared to a nonredundant database of the protein sequences
by PSI-BLAST. Whenever a pair member detects its pair-mate,
the positions that are aligned both in the sequential and
structural alignments are determined, and the alignment
sensitivity is expressed as the percentage of these positions
out of the structural alignment. Fifty-two sequences detected
their pair-mates (for 16 pairs the success was bi-directional
when either pair member was used as a query). The average
percentage of correctly aligned residues per structural
alignment was 43.5 ± 2.2%. Other properties of the
alignments were also examined, such as the sensitivity
vs. specificity and the change in these parameters over
consecutive iterations. Notably, there is an improvement
in alignment sensitivity over consecutive iterations, reaching
an average of 50.9 ± 2.5% within the five iterations
tested in the current study.