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Structural similarity to bridge sequence space: Finding new families on the bridges

Item Type:Article
Title:Structural similarity to bridge sequence space: Finding new families on the bridges
Creators Name:Shah, P.K. and Aloy, P. and Bork, P. and Russell, R.B.
Abstract:Structures for protein domains have increased rapidly in recent years owing to advances in structural biology and structural genomics projects. New structures are often similar to those solved previously, and such similarities can give insights into function by linking poorly understood families to those that are better characterized. They also allow the possibility of combing information to find still more proteins adopting a similar structure and sometimes a similar function, and to reprioritize families in structural genomics pipelines. We explore this possibility here by preparing merged profiles for pairs of structurally similar, but not necessarily sequence-similar, domains within the SMART and Pfam database by way of the Structural Classification of Proteins (SCOP). We show that such profiles are often able to successfully identify further members of the same superfamily and thus can be used to increase the sensitivity of database searching methods like HMMer and PSI-BLAST. We perform detailed benchmarks using the SMART and Pfam databases with four complete genomes frequently used as annotation benchmarks. We quantify the associated increase in structural information in Swissprot and discuss examples illustrating the applicability of this approach to understand functional and evolutionary relationships between protein families.
Keywords:Domain Family, Evolution, Protein Structure, Structural Genomics
Source:Protein Science
ISSN:0961-8368
Publisher:Cold Spring Harbor Laboratory Press (U.S.A.)
Volume:14
Number:5
Page Range:1305-1314
Date:1 January 2005
Official Publication:https://doi.org/10.1110/ps.041187405
PubMed:View item in PubMed

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