title: Correlated positions in protein evolution and engineering.
abstract: Statistical analysis of a protein multiple sequence alignment can reveal groups of positions that undergo interdependent mutations throughout evolution. At these so-called correlated positions, only certain combinations of amino acids appear to be viable for maintaining proper folding, stability, catalytic activity or specificity. Therefore, it is often speculated that they could be interesting guides for semi-rational protein engineering purposes. Because they are a fingerprint from protein evolution, their analysis may provide valuable insight into a protein's structure or function and furthermore, they may also be suitable target positions for mutagenesis. Unfortunately, little is currently known about the properties of these correlation networks and how they should be used in practice. This review summarises the recent findings, opportunities and pitfalls of the concept.
authors: Department of Biochemical and Microbial Technology, Centre for Industrial Biotechnology and Biocatalysis, Ghent University, Coupure Links 653, 9000, Ghent, Belgium.
authors: Jorick
authors: J
authors: Franceus
authors: Department of Biochemical and Microbial Technology, Centre for Industrial Biotechnology and Biocatalysis, Ghent University, Coupure Links 653, 9000, Ghent, Belgium.
authors: Tom
authors: T
authors: Verhaeghe
authors: Department of Biochemical and Microbial Technology, Centre for Industrial Biotechnology and Biocatalysis, Ghent University, Coupure Links 653, 9000, Ghent, Belgium. tom.desmet@ugent.be.
authors: Tom
authors: 0000-0002-5788-3022
authors: T
authors: Desmet
mesh_terms: D000596:Amino Acids / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019143:Evolution, Molecular; D016296:Mutagenesis; D015202:Protein Engineering; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D011506:Proteins
keywords: Coevolution; Correlated mutation analysis; Correlated positions; Protein engineering