Using Analyses of Amino Acid Coevolution to Understand Protein Structure and Function

被引:14
作者
Ashenberg, Orr [1 ,2 ]
Laub, Michael T. [1 ,2 ,3 ]
机构
[1] MIT, Dept Biol, Cambridge, MA 02139 USA
[2] MIT, Computat & Syst Biol Initiat, Cambridge, MA 02139 USA
[3] MIT, Howard Hughes Med Inst, Cambridge, MA USA
来源
METHODS IN PROTEIN DESIGN | 2013年 / 523卷
关键词
MULTIPLE SEQUENCE ALIGNMENT; STRUCTURE PREDICTION; RESIDUE COEVOLUTION; SPECIFICITY; MUTATIONS; EVOLUTION; INFORMATION; COVARIATION; PATHWAYS; SEARCH;
D O I
10.1016/B978-0-12-394292-0.00009-6
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Determining which residues of a protein contribute to a specific function is a difficult problem. Analyses of amino acid covariation within a protein family can serve as a useful guide by identifying residues that are functionally coupled. Covariation analyses have been successfully used on several different protein families to identify residues that work together to promote folding, enable protein protein interactions, or contribute to an enzymatic activity. Covariation is a statistical signal that can be measured in a multiple sequence alignment of homologous proteins. As sequence databases have expanded dramatically, covariation analyses have become easier and more powerful. In this chapter, we describe how functional covariation arises during the evolution of proteins and how this signal can be distinguished from various background signals. We discuss the basic methodology for performing amino acid covariation analysis, using bacterial two-component signal transduction proteins as an example. We provide practical suggestions for each step of the process including assembly of protein sequences, construction of a multiple sequence alignment measurement of covariation, and analysis of results.
引用
收藏
页码:191 / 212
页数:22
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