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Summary: Do Aligned Sequences Share the Same Fold?
Ruben A. Abagyan* and Serge Batalov
The Skirball Institute of
Biomolecular Medicine
Biochemistry Department
NYU Medical Center
540 First Avenue, New York
NY 10016, USA
Sequence comparison remains a powerful tool to assess the structural
relatedness of two proteins. To develop a sensitive sequence-based pro-
cedure for fold recognition, we performed an exhaustive global alignment
(with zero end gap penalties) between sequences of protein domains
with known three-dimensional folds. The subset of 1.3 million alignments
between sequences of structurally unrelated domains was used to derive
a set of analytical functions that represent the probability of structural
signi®cance for any sequence alignment at a given sequence identity,
sequence similarity and alignment score. Analysis of overlap between
structurally signi®cant and insigni®cant alignments shows that sequence
identity and sequence similarity measures are poor indicators of struc-
tural relatedness in the ``twilight zone'', while the alignment score allows
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