Assessment of a rigorous transitive profile based search method to detect remotely similar proteins

Chakrabarti, S. ; Abhinandan, K. R. ; Sowdhamini, R. ; Srinivasan, N. ; Sandhya, S. (2005) Assessment of a rigorous transitive profile based search method to detect remotely similar proteins Journal of Biomolecular Structure and Dynamics, 23 (3). pp. 283-298. ISSN 0739-1102

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Profile-based sequence search procedures are commonly employed to detect remote relationships between proteins. We provide an assessment of a Cascade PSI-BLAST protocol that rigorously employs intermediate sequences in detecting remote relationships between proteins. In this approach we detect using PSI-BLAST, which involves multiple rounds of iteration, an initial set of homologues for a protein in a ‘first generation’ search by querying a database. We propagate a ‘second generation’ search in the database, involving multiple runs of PSI-BLAST using each of the homologues identified in the previous generation as queries to recognize homologues not detected earlier. This non-directed search process can be viewed as an iteration of iterations that is continued to detect further homologues until no new hits are detectable. We present an assessment of the coverage of this ‘cascaded’ intermediate sequence search on diverse folds and find that searches for up to three generations detect most known homologues of a query. Our assessments show that this approach appears to perform better than the traditional use of PSI-BLAST by detecting 15% more relationships within a family and 35% more relationships within a superfamily. We show that such searches can be performed on generalized sequence databases and non-trivial relationships between proteins can be detected effectively. Such a propagation of searches maximizes the chances of detecting distant homologies by effectively scanning protein “fold space”.

Item Type:Article
Source:Copyright of this article belongs to Taylor and Francis Group.
Keywords:Database Searching; Homology Detection; Protein Evolution; Protein Structures; Sequence Analysis
ID Code:97572
Deposited On:13 Mar 2013 05:01
Last Modified:13 Mar 2013 05:01

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