title: Functional neighbors: inferring relationships between nonhomologous protein families using family-specific packing motifs.
abstract: We describe a new approach for inferring the functional relationships between nonhomologous protein families by looking at statistical enrichment of alternative function predictions in classification hierarchies such as Gene Ontology (GO) and Structural Classification of Proteins (SCOP). Protein structures are represented by robust graph representations, and the fast frequent subgraph mining algorithm is applied to protein families to generate sets of family-specific packing motifs, i.e., amino acid residue-packing patterns shared by most family members but infrequent in other proteins. The function of a protein is inferred by identifying in it motifs characteristic of a known family. We employ these family-specific motifs to elucidate functional relationships between families in the GO and SCOP hierarchies. Specifically, we postulate that two families are functionally related if one family is statistically enriched by motifs characteristic of another family, i.e., if the number of proteins in a family containing a motif from another family is greater than expected by chance. This function-inference method can help annotate proteins of unknown function, establish functional neighbors of existing families, and help specify alternate functions for known proteins.
authors.affiliation: Department of Computational and Structural Chemistry, GlaxoSmithKline, Collegeville, PA UP12-210, USA. deepak.2.bandyopadhyay@gsk.com
authors.forename: Deepak
authors.initials: D
authors.lastname: Bandyopadhyay
authors.forename: Jun
authors.initials: J
authors.lastname: Huan
authors.forename: Jinze
authors.initials: J
authors.lastname: Liu
authors.forename: Jan
authors.initials: J
authors.lastname: Prins
authors.forename: Jack
authors.initials: J
authors.lastname: Snoeyink
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Alexander
authors.initials: A
authors.lastname: Tropsha
mesh_terms: D000465:Algorithms; D019295:Computational Biology / Q000379:methods*; D057225:Data Mining / Q000379:methods*; D023281:Genomics / Q000379:methods; D008958:Models, Molecular; D009249:NADP / Q000737:chemistry; D009687:Nuclear Proteins / Q000737:chemistry; D010749:Phosphoprotein Phosphatases / Q000737:chemistry; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D011506:Proteins / Q000737:chemistry* / Q000145:classification
chemical_list: D009687:Nuclear Proteins; D011506:Proteins; D009249:NADP; D010749:Phosphoprotein Phosphatases