Computational design, construction, and characterization of a set of specificity determining residues in protein-protein interactions.
Proteins interact with different partners to perform different functions and it is important to elucidate the determinants of partner specificity in protein complex formation. Although methods for detecting specificity determining positions have been developed previously, direct experimental evidence for these amino acid residues is scarce, and the lack of information has prevented further computational studies. In this article, we constructed a dataset that is likely to exhibit specificity in protein complex formation, based on available crystal structures and several intuitive ideas about interaction profiles and functional subclasses. We then defined a "structure-based specificity determining position (sbSDP)" as a set of equivalent residues in a protein family showing a large variation in their interaction energy with different partners. We investigated sequence and structural features of sbSDPs and demonstrated that their amino acid propensities significantly differed from those of other interacting residues and that the importance of many of these residues for determining specificity had been verified experimentally.
National Institute of Biomedical Innovation, Ibaraki, Osaka, Japan. chio@nibio.go.jp
Chioko
C
Nagao
Nozomi
N
Izako
Shinji
S
Soga
Samia Haseeb
SH
Khan
Shigeki
S
Kawabata
Hiroki
H
Shirai
Kenji
K
Mizuguchi
D000595:Amino Acid Sequence; D000818:Animals; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods*; D030562:Databases, Protein; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping / Q000379:methods*; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein / Q000379:methods*; D013816:Thermodynamics; D016212:Transforming Growth Factor beta
D011506:Proteins; D016212:Transforming Growth Factor beta