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Structural dynamics flexibility informs function and evolution at a proteome scale

Nevin Gerek, Z
; 
Kumar, S
; 
Banu Ozkan, S
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Journal Article
Date
2013-04-01
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Subject
elastic network models
 functional genomics
 single nucleotide variants
 structural dynamics
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http://hdl.handle.net/20.500.12613/5410
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Structural dynamics flexibility informs function and evolution at a proteome scale.pdf
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DOI
10.1111/eva.12052
Abstract
Protein structures are dynamic entities with a myriad of atomic fluctuations, side-chain rotations, and collective domain movements. Although the importance of these dynamics to proper functioning of proteins is emerging in the studies of many protein families, there is a lack of broad evidence for the critical role of protein dynamics in shaping the biological functions of a substantial fraction of residues for a large number of proteins in the human proteome. Here, we propose a novel dynamic flexibility index (dfi) to quantify the dynamic properties of individual residues in any protein and use it to assess the importance of protein dynamics in 100 human proteins. Our analyses involving functionally critical positions, disease-associated and putatively neutral population variations, and the rate of interspecific substitutions per residue produce concordant patterns at a proteome scale. They establish that the preservation of dynamic properties of residues in a protein structure is critical for maintaining the protein/biological function. Therefore, structural dynamics needs to become a major component of the analysis of protein function and evolution. Such analyses will be facilitated by the dfi, which will also enable the integrative use of structural dynamics with evolutionary conservation in genomic medicine as well as functional genomics investigations. © 2013 The Authors. Published by Blackwell Publishing Ltd.
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Evolutionary Applications
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