title: A graph-theoretic approach to the identification of three-dimensional patterns of amino acid side-chains in protein structures.
abstract: This paper discusses the use of graph-theoretic methods for the representation and searching of three-dimensional patterns of side-chains in protein structures. The position of a side-chain is represented by pseudo-atoms, and the relative positions of pairs of side-chains by the distances between them. This description of the geometry can be represented by a labelled graph in which the nodes and the edges of the graph represent the pseudo-atoms and the sets of inter-pseudo-atomic distances, respectively. Given such a representation, a protein can be searched for the presence of a user-defined query pattern of side-chains by means of a subgraph-isomorphism algorithm which is implemented in the program ASSAM. Experiments with one such algorithm, that due to Ullmann, show that it provides both an effective and a highly efficient way of searching for patterns of side-chains. The method is illustrated by searches for the serine protease catalytic triad, for residues involved in the catalytic activity of staphyloccocal nuclease, and for the zinc-binding side-chains of thermolysin. The catalytic triad pattern search revealed the existence of a second Asp-His-Ser triad-like arrangement of residues in trypsinogen and chymotrypsinogen, in addition to the catalytic residues. In addition the program can be used to search for hypothetical patterns, as is shown for a pattern of three tryptophan side-chains. These searches demonstrate that the search algorithm can successfully retrieve the great majority of the expected proteins, as well as other, previously unreported proteins that contain the pattern of interest.
authors.affiliation: Krebs Institute for Biomolecular Research Department of Molecular Biology and Biotechnology, University of Sheffield, Western Bank, U.K.
authors.forename: P J
authors.initials: PJ
authors.lastname: Artymiuk
authors.forename: A R
authors.initials: AR
authors.lastname: Poirrette
authors.forename: H M
authors.initials: HM
authors.lastname: Grindley
authors.forename: D W
authors.initials: DW
authors.lastname: Rice
authors.forename: P
authors.initials: P
authors.lastname: Willett
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry*; D002919:Chymotrypsinogen / Q000737:chemistry; D003196:Computer Graphics; D016208:Databases, Factual; D008836:Micrococcal Nuclease / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D012697:Serine Endopeptidases / Q000737:chemistry; D012984:Software; D013820:Thermolysin / Q000737:chemistry; D014362:Trypsinogen / Q000737:chemistry; D014364:Tryptophan / Q000737:chemistry; D015032:Zinc / Q000378:metabolism
chemical_list: D000596:Amino Acids; D011506:Proteins; D014364:Tryptophan; D014362:Trypsinogen; D002919:Chymotrypsinogen; D008836:Micrococcal Nuclease; D012697:Serine Endopeptidases; D013820:Thermolysin; D015032:Zinc