Secondary structure‐based profiles: Use of structure‐conserving scoring tables in searching protein sequence databases for structural similarities

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Abstract
The profile method, for detecting distantly related proteins by sequence comparison, has been extended to incorporate secondary structure information from know X‐ray structures. The sequence of a known structure is aligned to sequences of other members of a given folding class. From the known structure, the secondary structure (α‐helix, β‐strand or “other”) is assigned to each position of the aligned sequences. As in the standard profile method,1 a position‐dependent scoring table, termed a profile, is calculated from the aligned sequences. However, rather than using the standard Dayhoff mutation table in calculating the profile, we use distinct amino acid mutation tables for residues in α‐helices, β‐strands or other secondary structures to calculate the profile. In addition, we also distinguish between internal and external residues. With this new secondary structure‐based profile method, we created a profile for eight‐stranded, antiparallel β barrels of the insecticyanin folding class. It is based on the sequences of retinol‐binding protein, insecticyanin and β‐lactoglobulin. Scanning the sequence database with this profile, it was possible to detect the sequence of avidin. The structure of streptavidin is known, and it appears to be distantly related to the antiparallel β barrels. Also detected is the sequence of complement component C8, which we therefore predict to be a member of this folding class.