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Small‐world network approach to identify key residues in protein–protein interaction
Author(s) -
del Sol Antonio,
O'Meara Paul
Publication year - 2004
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.20348
Subject(s) - hot spot (computer programming) , amino acid residue , protein–protein interaction , monomer , chemistry , protein structure , sequence (biology) , biological system , computational biology , crystallography , biophysics , peptide sequence , biology , biochemistry , computer science , polymer , organic chemistry , operating system , gene
We show that protein complexes can be represented as small‐world networks, exhibiting a relatively small number of highly central amino‐acid residues occurring frequently at protein–protein interfaces. We further base our analysis on a set of different biological examples of protein–protein interactions with experimentally validated hot spots, and show that 83% of these predicted highly central residues, which are conserved in sequence alignments and nonexposed to the solvent in the protein complex, correspond to or are in direct contact with an experimentally annotated hot spot. The remaining 17% show a general tendency to be close to an annotated hot spot. On the other hand, although there is no available experimental information on their contribution to the binding free energy, detailed analysis of their properties shows that they are good candidates for being hot spots. Thus, highly central residues have a clear tendency to be located in regions that include hot spots. We also show that some of the central residues in the protein complex interfaces are central in the monomeric structures before dimerization and that possible information relating to hot spots of binding free energy could be obtained from the unbound structures. Proteins 2005. © 2004 Wiley‐Liss, Inc.