Identifying functionally important cis-peptide containing segments in proteins and their utility in molecular function annotation

Das, Sreetama and Ramakumar, Suryanarayanarao and Pal, Debnath (2014) Identifying functionally important cis-peptide containing segments in proteins and their utility in molecular function annotation. In: FEBS JOURNAL, 281 (24). pp. 5602-5621.

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Abstract

Cis-peptide embedded segments are rare in proteins but often highlight their important role in molecular function when they do occur. The high evolutionary conservation of these segments illustrates this observation almost universally, although no attempt has been made to systematically use this information for the purpose of function annotation. In the present study, we demonstrate how geometric clustering and level-specific Gene Ontology molecular-function terms (also known as annotations) can be used in a statistically significant manner to identify cis-embedded segments in a protein linked to its molecular function. The present study identifies novel cis-peptide fragments, which are subsequently used for fragment-based function annotation. Annotation recall benchmarks interpreted using the receiver-operator characteristic plot returned an area-under-curve >0.9, corroborating the utility of the annotation method. In addition, we identified cis-peptide fragments occurring in conjunction with functionally important trans-peptide fragments, providing additional insights into molecular function. We further illustrate the applicability of our method in function annotation where homology-based annotation transfer is not possible. The findings of the present study add to the repertoire of function annotation approaches and also facilitate engineering, design and allied studies around the cis-peptide neighborhood of proteins.

Item Type:	Journal Article
Publication:	FEBS JOURNAL
Additional Information:	Copyright for this article belongs to the WILEY-BLACKWELL, 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
Department/Centre:	Division of Interdisciplinary Sciences > Supercomputer Education & Research Centre Division of Physical & Mathematical Sciences > Physics
Date Deposited:	18 Jan 2015 06:05
Last Modified:	18 Jan 2015 06:05
URI:	http://eprints.iisc.ac.in/id/eprint/50677

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