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Evolutionary and structural feedback on selection of sequences for comparative analysis of proteins
Author(s) -
Mihalek I.,
Reš I.,
Lichtarge O.
Publication year - 2006
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.20866
Subject(s) - protein superfamily , computational biology , selection (genetic algorithm) , sequence (biology) , set (abstract data type) , biology , divergence (linguistics) , cluster (spacecraft) , protein evolution , multiple sequence alignment , threading (protein sequence) , protein structure , sequence alignment , computer science , evolutionary biology , genetics , peptide sequence , artificial intelligence , gene , biochemistry , linguistics , philosophy , programming language
It has been noted that slowly evolving protein residues have two properties: (a) they tend to cluster in the native fold, and (b) they delineate functional surfaces—parts of the surface through which the protein interacts with other proteins or small ligands. Herein, we demonstrate that the two are coupled sufficiently strongly that one effect, when observed, statistically implies the other. Detection of both can be accomplished in multiple sequence alignment related methods by the careful selection of relevant sequences. For the demonstration, we use two sets of protein families: a small set of diverse proteins with diverse functional surfaces, and a large set of homodimerizing enzymes. A practical outcome of our considerations is a simple prescriptive rule for the selection of homologous sequences for the comparative analysis of proteins: in order to optimize the detection of (potentially unknown) functional surfaces, it is sufficient to select sequences in such a way that the residues observed at any level of evolutionary divergence, as implied by the alignment, cluster on the folded protein. Proteins 2006. © 2006 Wiley‐Liss, Inc.