title: Dissecting protein loops with a statistical scalpel suggests a functional implication of some structural motifs.
abstract: BACKGROUND
  One of the strategies for protein function annotation is to search particular structural motifs that are known to be shared by proteins with a given function.
  
  
  RESULTS
  Here, we present a systematic extraction of structural motifs of seven residues from protein loops and we explore their correspondence with functional sites. Our approach is based on the structural alphabet HMM-SA (Hidden Markov Model - Structural Alphabet), which allows simplification of protein structures into uni-dimensional sequences, and advanced pattern statistics adapted to short sequences. Structural motifs of interest are selected by looking for structural motifs significantly over-represented in SCOP superfamilies in protein loops. We discovered two types of structural motifs significantly over-represented in SCOP superfamilies: (i) ubiquitous motifs, shared by several superfamilies and (ii) superfamily-specific motifs, over-represented in few superfamilies. A comparison of ubiquitous words with known small structural motifs shows that they contain well-described motifs as turn, niche or nest motifs. A comparison between superfamily-specific motifs and biological annotations of Swiss-Prot reveals that some of them actually correspond to functional sites involved in the binding sites of small ligands, such as ATP/GTP, NAD(P) and SAH/SAM.
  
  
  CONCLUSIONS
  Our findings show that statistical over-representation in SCOP superfamilies is linked to functional features. The detection of over-represented motifs within structures simplified by HMM-SA is therefore a promising approach for prediction of functional sites and annotation of uncharacterized proteins.
authors.affiliation: INSERM, U973, Paris F-75013, France.
authors.forename: Leslie
authors.initials: L
authors.lastname: Regad
authors.forename: Juliette
authors.initials: J
authors.lastname: Martin
authors.forename: Anne-Claude
authors.initials: AC
authors.lastname: Camproux
mesh_terms: D020816:Amino Acid Motifs; D030562:Databases, Protein; D008024:Ligands; D008390:Markov Chains; D008958:Models, Molecular; D058977:Molecular Sequence Annotation / Q000379:methods*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D008024:Ligands; D011506:Proteins