title: Protein comparison at the domain architecture level.
abstract: BACKGROUND
  The general method used to determine the function of newly discovered proteins is to transfer annotations from well-characterized homologous proteins. The process of selecting homologous proteins can largely be classified into sequence-based and domain-based approaches. Domain-based methods have several advantages for identifying distant homology and homology among proteins with multiple domains, as compared to sequence-based methods. However, these methods are challenged by large families defined by 'promiscuous' (or 'mobile') domains.
  
  
  RESULTS
  Here we present a measure, called Weighed Domain Architecture Comparison (WDAC), of domain architecture similarity, which can be used to identify homolog of multidomain proteins. To distinguish these promiscuous domains from conventional protein domains, we assigned a weight score to Pfam domain extracted from RefSeq proteins, based on its abundance and versatility. To measure the similarity of two domain architectures, cosine similarity (a similarity measure used in information retrieval) is used. We combined sequence similarity with domain architecture comparisons to identify proteins belonging to the same domain architecture. Using human and nematode proteomes, we compared WDAC with an unweighted domain architecture method (DAC) to evaluate the effectiveness of domain weight scores. We found that WDAC is better at identifying homology among multidomain proteins.
  
  
  CONCLUSIONS
  Our analysis indicates that considering domain weight scores in domain architecture comparisons improves protein homology identification. We developed a web-based server to allow users to compare their proteins with protein domain architectures.
authors: Korean BioInformation Center, KRIBB, Daejeon 305-806, Korea. bulee@kribb.re.kr
authors: Byungwook
authors: B
authors: Lee
authors: Doheon
authors: D
authors: Lee
mesh_terms: D019295:Computational Biology / Q000379:methods*; D030562:Databases, Protein; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry*; D020539:Sequence Analysis, Protein
chemical_list: D011506:Proteins