An automatic method involving cluster analysis of secondary structures for the identification of domains in proteins

Abstract

With a growing number of structures available in the Brookhaven Protein Data Bank, automatic methods for domain identification are required for the construction of databases. Domains are considered to be clusters of secondary structure elements. Thus, helices and strands are first clustered using intersecondary structural distances between Ca positions, and dendrograms based on this distance measure are used to identify domains. Individual domains are recognized by a disjoint factor, which enables the automatic identification and cIassification into disjoint, interacting, and conjoint domains. Application to a database of 83 protein families and 18 unique structures shows that the approach provides an effective delineation of boundaries and identifies those proteins that can be considered as a single domain. A quantitative estimate of the interaction between domains has been proposed. The database of protein domains is a useful tool for understanding protein folding, for recognizing protein folds, and for understanding structure-activity relationships.

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

“…These approaches maximize the number of contacts within a domain. Some authors have proposed alternative methods to hierarchically split proteins into compact units [70][71][72][73][74][75][76]. These folding units are supposed to fold independently during the folding process, creating structural modules which are assembled to give the native structure.…”

Analysis of protein contacts into Protein Units

“…As noted early by Wetlaufer, some protein domains are not sequential [50]. Comparison with other related approaches such as DIAL would be also quite interesting [45]. In the same way, behavior of Protein Peeling can be compared to protein domain assignment, e.g.…”

“…Some authors have proposed different methods to hierarchically split proteins into compact units smaller than protein domains [15,[45][46][47][48]. In this field, we should notice the most advanced research, namely DIAL [45,47] and his accompanying database [49].…”

“…In this field, we should notice the most advanced research, namely DIAL [45,47] and his accompanying database [49]. In this method, domains are considered to be clusters of secondary structure elements.…”

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

“…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.…”