title: Engineering proteins for thermostability through rigidifying flexible sites.
abstract: Engineering proteins for thermostability is an exciting and challenging field since it is critical for broadening the industrial use of recombinant proteins. Thermostability of proteins arises from the simultaneous effect of several forces such as hydrophobic interactions, disulfide bonds, salt bridges and hydrogen bonds. All of these interactions lead to decreased flexibility of polypeptide chain. Structural studies of mesophilic and thermophilic proteins showed that the latter need more rigid structures to compensate for increased thermal fluctuations. Hence flexibility can be an indicator to pinpoint weak spots for enhancing thermostability of enzymes. A strategy has been proven effective in enhancing proteins' thermostability with two steps: predict flexible sites of proteins firstly and then rigidify these sites. We refer to this approach as rigidify flexible sites (RFS) and give an overview of such a method through summarizing the methods to predict flexibility of a protein, the methods to rigidify residues with high flexibility and successful cases regarding enhancing thermostability of proteins using RFS.
authors.affiliation: Department of Biochemical Engineering, School of Chemical Engineering and Technology, Key Laboratory of Systems Bioengineering, Ministry of Education, Tianjin University, Tianjin 300072, China.
authors.forename: Haoran
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Biochemical Engineering, School of Chemical Engineering and Technology, Key Laboratory of Systems Bioengineering, Ministry of Education, Tianjin University, Tianjin 300072, China. Electronic address: huang@tju.edu.cn.
authors.forename: He
authors.initials: H
authors.lastname: Huang
mesh_terms: D006358:Hot Temperature; D018583:Pliability; D011487:Protein Conformation; D015202:Protein Engineering; D055550:Protein Stability; D011994:Recombinant Proteins
chemical_list: D011994:Recombinant Proteins
keywords: Biocatalyst; Flexible sites; Protein engineering; Rational design; Thermostability