Consensus protein design.
A popular and successful strategy in semi-rational design of protein stability is the use of evolutionary information encapsulated in homologous protein sequences. Consensus design is based on the hypothesis that at a given position, the respective consensus amino acid contributes more than average to the stability of the protein than non-conserved amino acids. Here, we review the consensus design approach, its theoretical underpinnings, successes, limitations and challenges, as well as providing a detailed guide to its application in protein engineering.
Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Faculty of Medicine, Monash University, Clayton, Victoria 3800, Australia Medical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
Benjamin T
BT
Porebski
Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Faculty of Medicine, Monash University, Clayton, Victoria 3800, Australia ashley.buckle@monash.edu.
Ashley M
AM
Buckle
D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D048088:Informatics / Q000379:methods; D015202:Protein Engineering / Q000379:methods; D055550:Protein Stability; D011506:Proteins / Q000737:chemistry* / Q000235:genetics; D016415:Sequence Alignment; D013696:Temperature; D013816:Thermodynamics
D011506:Proteins
consensus design; multiple sequence alignment; protein stability; semi-rational design; statistical sequence analysis; thermostability