Molecular Dynamics Information Improves cis-Peptide-Based Function Annotation of Proteins

Das, Sreetama and Bhadra, Pratiti and Ramakumar, Suryanarayanarao and Pal, Debnath (2017) Molecular Dynamics Information Improves cis-Peptide-Based Function Annotation of Proteins. In: JOURNAL OF PROTEOME RESEARCH, 16 (8). pp. 2936-2946.

PDF Jou_Pro_Res_16-8_2936_2017.pdf - Published Version Restricted to Registered users only Download (4MB) | Request a copy

Abstract

cis-Peptide bonds, whose occurrence in proteins is rare but evolutionarily conserved, are implicated to play an important role in protein function. This has led to their previous use in a homology-independent, fragment-match-based protein function annotation method. However, proteins are not static molecules; dynamics is integral to their activity. This is nicely epitomized by the geometric isomerization of cis-peptide to trans form for molecular activity. Hence we have incorporated both static (cis-peptide) and dynamics information to improve the prediction of protein molecular function. Our results show that cis-peptide information alone cannot detect functional matches in cases where cis-trans isomerization exists but 3D coordinates have been obtained for only the trans isomer or when the cis-peptide bond is incorrectly assigned as trans. On the contrary, use of dynamics information alone includes false-positive matches for cases where fragments with similar secondary structure show similar dynamics, but the proteins do not share a common function. Combining the two methods reduces errors while detecting the true matches, thereby enhancing the utility of our method in function annotation. A combined approach, therefore, opens up new avenues of improving existing automated function annotation methodologies.

Item Type:	Journal Article
Publication:	JOURNAL OF PROTEOME RESEARCH
Additional Information:	Copy right for this article belongs to the AMER CHEMICAL SOC, 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
Department/Centre:	Division of Interdisciplinary Sciences > Supercomputer Education & Research Centre Division of Physical & Mathematical Sciences > Physics
Date Deposited:	01 Sep 2017 09:17
Last Modified:	01 Sep 2017 09:17
URI:	http://eprints.iisc.ac.in/id/eprint/57713

Actions (login required)

View Item