Profile analysis: detection of distantly related proteins.

TLDR

Profile analysis detects distantly related proteins by comparing sequences to a profile that incorporates Dayhoff mutational distances, structural study results, and alignment information from protein families. The method builds a position‑specific scoring table from an aligned group of sequences and tests a target sequence against this profile using dynamic programming, allowing any number of known sequences to contribute information and incorporating position‑specific insertion/deletion penalties that reflect secondary structure. Tests with globin and immunoglobulin sequences show that profile analysis can distinguish all members of these families from all other sequences in a database of 3,800 proteins.

Abstract

Profile analysis is a method for detecting distantly related proteins by sequence comparison. The basis for comparison is not only the customary Dayhoff mutational-distance matrix but also the results of structural studies and information implicit in the alignments of the sequences of families of similar proteins. This information is expressed in a position-specific scoring table (profile), which is created from a group of sequences previously aligned by structural or sequence similarity. The similarity of any other sequence (target) to the group of aligned sequences (probe) can be tested by comparing the target to the profile using dynamic programming algorithms. The profile method differs in two major respects from methods of sequence comparison in common use: (i) Any number of known sequences can be used to construct the profile, allowing more information to be used in the testing of the target than is possible with pairwise alignment methods. (ii) The profile includes the penalties for insertion or deletion at each position, which allow one to include the probe secondary structure in the testing scheme. Tests with globin and immunoglobulin sequences show that profile analysis can distinguish all members of these families from all other sequences in a database containing 3800 protein sequences.