Protein domain identification and improved sequence similarity searching using PSI‐BLAST

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Abstract
Protein sequences containing more than one structural domain are problematic when used in homology searches where they can either stop an iterative database search prematurely or cause an explosion of a search to common domains. We describe a method, DOMAINATION, that infers domains and their boundaries in a query sequence from local gapped alignments generated using PSI‐BLAST. Through a new technique to recognize domain insertions and permutations, DOMAINATION submits delineated domains as successive database queries in further iterative steps. Assessed over a set of 452 multidomain proteins, the method predicts structural domain boundaries with an overall accuracy of 50% and improves finding distant homologies by 14% compared with PSI‐BLAST. DOMAINATION is available as a web based tool at http://mathbio.nimr.mrc.ac.uk, and the source code is available from the authors upon request. Proteins 2002;48:672–681.