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Definition of the tempo of sequence diversity across an alignment and automatic identification of sequence motifs: Application to protein homologous families and superfamilies
Author(s) -
May Alex C.W.
Publication year - 2002
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.0211202
Subject(s) - protein superfamily , sequence (biology) , sequence alignment , computational biology , protein family , multiple sequence alignment , protein sequencing , partition (number theory) , sequence motif , biology , sequence logo , protein structure , set (abstract data type) , protein function prediction , constraint (computer aided design) , sequence analysis , genetics , peptide sequence , computer science , protein function , mathematics , combinatorics , gene , biochemistry , geometry , programming language
Abstract It is often possible to identify sequence motifs that characterize a protein family in terms of its fold and/or function from aligned protein sequences. Such motifs can be used to search for new family members. Partitioning of sequence alignments into regions of similar amino acid variability is usually done by hand. Here, I present a completely automatic method for this purpose: one that is guaranteed to produce globally optimal solutions at all levels of partition granularity. The method is used to compare the tempo of sequence diversity across reliable three‐dimensional (3D) structure‐based alignments of 209 protein families (HOMSTRAD) and that for 69 superfamilies (CAMPASS). (The mean alignment length for HOMSTRAD and CAMPASS are very similar.) Surprisingly, the optimal segmentation distributions for the closely related proteins and distantly related ones are found to be very similar. Also, optimal segmentation identifies an unusual protein superfamily. Finally, protein 3D structure clues from the tempo of sequence diversity across alignments are examined. The method is general, and could be applied to any area of comparative biological sequence and 3D structure analysis where the constraint of the inherent linear organization of the data imposes an ordering on the set of objects to be clustered.