title: Efficient and automated large-scale detection of structural relationships in proteins with a flexible aligner.
abstract: BACKGROUND
  The total number of known three-dimensional protein structures is rapidly increasing. Consequently, the need for fast structural search against complete databases without a significant loss of accuracy is increasingly demanding. Recently, TopSearch, an ultra-fast method for finding rigid structural relationships between a query structure and the complete Protein Data Bank (PDB), at the multi-chain level, has been released. However, comparable accurate flexible structural aligners to perform efficient whole database searches of multi-domain proteins are not yet available. The availability of such a tool is critical for a sustainable boosting of biological discovery.
  
  
  RESULTS
  Here we report on the development of a new method for the fast and flexible comparison of protein structure chains. The method relies on the calculation of 2D matrices containing a description of the three-dimensional arrangement of secondary structure elements (angles and distances). The comparison involves the matching of an ensemble of substructures through a nested-two-steps dynamic programming algorithm. The unique features of this new approach are the integration and trade-off balancing of the following: 1) speed, 2) accuracy and 3) global and semiglobal flexible structure alignment by integration of local substructure matching. The comparison, and matching with competitive accuracy, of one medium sized (250-aa) query structure against the complete PDB database (216,322 protein chains) takes about 8 min using an average desktop computer. The method is at least 2-3 orders of magnitude faster than other tested tools with similar accuracy. We validate the performance of the method for fold and superfamily assignment in a large benchmark set of protein structures. We finally provide a series of examples to illustrate the usefulness of this method and its application in biological discovery.
  
  
  CONCLUSIONS
  The method is able to detect partial structure matching, rigid body shifts, conformational changes and tolerates substantial structural variation arising from insertions, deletions and sequence divergence, as well as structural convergence of unrelated proteins.
authors.affiliation: Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Alameda 340, Santiago, Chile.|Centre for Organismal Studies (COS), Heidelberg University, Heidelberg, Germany.
authors.forename: Fernando I
authors.initials: FI
authors.lastname: Gutiérrez
authors.affiliation: Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Alameda 340, Santiago, Chile.
authors.forename: Felipe
authors.initials: F
authors.lastname: Rodriguez-Valenzuela
authors.affiliation: Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Alameda 340, Santiago, Chile.|Centro Andaluz de Biología del Desarrollo (CABD), Universidad Pablo de Olavide, Sevilla, Spain.
authors.forename: Ignacio L
authors.initials: IL
authors.lastname: Ibarra
authors.affiliation: Centre for Organismal Studies (COS), Heidelberg University, Heidelberg, Germany. damienpdevos@gmail.com.|Centro Andaluz de Biología del Desarrollo (CABD), Universidad Pablo de Olavide, Sevilla, Spain. damienpdevos@gmail.com.
authors.forename: Damien P
authors.initials: DP
authors.lastname: Devos
authors.affiliation: Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Alameda 340, Santiago, Chile. fmelo@bio.puc.cl.
authors.forename: Francisco
authors.initials: F
authors.lastname: Melo
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D002138:Calibration; D019295:Computational Biology; D030562:Databases, Protein; D015321:Gene Rearrangement; D006801:Humans; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*
chemical_list: D011506:Proteins