Structural dynamics flexibility informs function and evolution at a proteome scale

Evolutionary Applications

Zeynep Nevin Gerek¹  Sudhir Kumar¹ 

[1] Center for Evolutionary Medicine and Informatics, Biodesign Institute, Arizona State University, Tempe, AZ, USA

关键词: elastic network models;    functional genomics;    single nucleotide variants;    structural dynamics;   

DOI  :  10.1111/eva.12052

来源: Wiley

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2013 The Authors. Evolutionary Applications. Published by Blackwell Publishing Ltd.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.