title: Structure-based function inference using protein family-specific fingerprints.
abstract: We describe a method to assign a protein structure to a functional family using family-specific fingerprints. Fingerprints represent amino acid packing patterns that occur in most members of a family but are rare in the background, a nonredundant subset of PDB; their information is additional to sequence alignments, sequence patterns, structural superposition, and active-site templates. Fingerprints were derived for 120 families in SCOP using Frequent Subgraph Mining. For a new structure, all occurrences of these family-specific fingerprints may be found by a fast algorithm for subgraph isomorphism; the structure can then be assigned to a family with a confidence value derived from the number of fingerprints found and their distribution in background proteins. In validation experiments, we infer the function of new members added to SCOP families and we discriminate between structurally similar, but functionally divergent TIM barrel families. We then apply our method to predict function for several structural genomics proteins, including orphan structures. Some predictions have been corroborated by other computational methods and some validated by subsequent functional characterization.
authors.affiliation: Department of Computer Science, University of North Carolina at Chapel Hill, North Carolina 27599, USA.
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: D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015203:Reproducibility of Results; D012984:Software; D013329:Structure-Activity Relationship
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D011506:Proteins; C511248:YcdX protein, E coli