DDOMAIN: Dividing structures into domains using a normalized domain–domain interaction profile

Abstract

Dividing protein structures into domains is proven useful for more accurate structural and functional characterization of proteins. Here, we develop a method, called DDOMAIN, that divides structure into DOMAINs using a normalized contact-based domain-domain interaction profile. Results of DDOMAIN are compared to AUTHORS annotations (domain definitions are given by the authors who solved protein structures), as well as to popular SCOP and CATH annotations by human experts and automatic programs. DDOMAIN's automatic annotations are most consistent with the AUTHORS annotations (90% agreement in number of domains and 88% agreement in both number of domains and at least 85% overlap in domain assignment of residues) if its three adjustable parameters are trained by the AUTHORS annotations. By comparison, the agreement is 83% (81% with at least 85% overlap criterion) between SCOP-trained DDOMAIN and SCOP annotations and 77% (73%) between CATH-trained DDOMAIN and CATH annotations. The agreement between DDOMAIN and AUTHORS annotations goes beyond single-domain proteins (97%, 82%, and 56% for single-, two-, and three-domain proteins, respectively). For an ''easy'' data set of proteins whose CATH and SCOP annotations agree with each other in number of domains, the agreement is 90% (89%) between ''easy-set''-trained DDOMAIN and CATH/SCOP annotations. The consistency between SCOP-trained DDOMAIN and SCOP annotations is superior to two other recently developed, SCOP-trained, automatic methods PDP (protein domain parser), and DomainParser 2. We also tested a simple consensus method made of PDP, DomainParser 2, and DDOMAIN and a different version of DDOMAIN based on a more sophisticated statistical energy function. The DDOMAIN server and its executable are available in the services section on http://sparks.informatics.iupui.edu.Keywords: structure/function studies; structural proteins; new methods; domain parser Proteins are made of single or multiple functional domains that can fold and function independently. Dividing a protein into domains is useful for more accurate function and structure determination because the methods for phylogenetic analysis and protein modeling usually work best for single domains (Ponting and Russell 2002). Both sequencebased (Chivian et al. 2003;Heger and Holm 2003;Linding et al. 2003;Bateman et al. 2004;Letunic et al. 2004;Liu and Rost 2004;Nagarajan and Yona 2004;von Ohsen et al. 2004;Sim et al. 2005) and structure-based methods (Holm and Sander 1994;Siddiqui and Barton 1995;Sowdhamini and Blundell 1995;Swindells 1995;Holm and Sander 1998;Taylor 1999;Xu et al. 2000;Alexandrov and Shindyalov 2003;Guo et al. 2003;Kundu et al. 2004) have been developed for identification of protein domains.The problem of dividing a protein structure into domains is not yet solved. This is in part due to the lack of an unambiguous definition of domains. In general,

An ambiguity principle for assigning protein structural domains

“…Hence, domain assignment is achieved using different representations of the protein structure, such as maps, graphs ( 43 – 45 ), or Gaussian network models ( 46 ). Although maximizing the ratio of intradomain contacts over domain-domain interface is the most popular approach ( 47 – 50 ), other criteria have also been used successfully, such as energy ( 51 ) or secondary structure ( 52 ). …”

Protein contacts, inter-residue interactions and side-chain modelling

“…Hence, methods for phylogenetic analyses and protein modelling usually perform better for single domains [58]. Automatic domain parsing generally makes the assumption that interdomain interaction (under a correct domain assignment) is weaker than the intradomain interaction (PUU [59], DOMAK [60] and 3Dee [61,62], DETECTIVE [63], DALI [64], STRUDL [65], DomainParser [66,67], Protein Domain Parser [68] and DDOMAIN [69]). These approaches maximize the number of contacts within a domain.…”

Evaluation system and web infrastructure for the second cryo-EM model challenge

“…Targets are split into domains by consulting the DomainParser (Guo et al, 2003), DDomain2 (Zhou et al, 2007) programs, and the ECOD (Cheng et al, 2014) database of structural domains. Organization of the web resource for the Domains evaluation is similar to that for the Monomers .…”