title: 3-D lookup: fast protein structure database searches at 90% reliability.
abstract: There are far fewer classes of three-dimensional protein folds than sequence families but the problem of detecting three-dimensional similarities is NP-complete. We present a novel heuristic for identifying 3-D similarities between a query structure and the database of known protein structures. Many methods for structure alignment use a bottom-up approach, identifying first local matches and then solving a combinatorial problem in building up larger clusters of matching substructures. Here, the top-down approach is to start with the global comparison and select a rough superimposition using a fast 3-D lookup of secondary structure motifs. The superimposition is then extended to an alignment of C alpha atoms by an iterative dynamic programming step. An all-against-all comparison of 385 representative proteins (150,000 pair comparisons) took 1 day of computer time on a single R8000 processor. In other words, one query structure is scanned against the database in a matter of minutes. The method is rated at 90% reliability at capturing statistically significant similarities. It is useful as a rapid preprocessor to a comprehensive protein structure database search system.
authors.affiliation: European Molecular Biology Laboratory, Heidelberg, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Holm
authors.forename: C
authors.initials: C
authors.lastname: Sander
mesh_terms: D000595:Amino Acid Sequence; D016282:Aspartic Acid Endopeptidases / Q000737:chemistry; D000081247:CSK Tyrosine-Protein Kinase; D016208:Databases, Factual; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011505:Protein-Tyrosine Kinases / Q000737:chemistry; D011506:Proteins / Q000737:chemistry*; D015203:Reproducibility of Results; D017386:Sequence Homology, Amino Acid; D019061:src-Family Kinases
chemical_list: D011506:Proteins; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; D016282:Aspartic Acid Endopeptidases