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Paper   IPM / Biological Sciences / 17053
School of Biological Sciences
  Title:   Thermal stability enhancement: Fundamental concepts of protein engineering strategies to manipulate the flexible structure
1.  Mahdie Rahban
2.  Samaneh Zolghadri
3.  Najmeh Salehi
4.  Faizan Ahmad
5.  Thomas Haertlé
6.  Nasrollah Rezaei-Ghaleh
7.  Lindsay Sawyer
8.  Ali Akbar Saboury
  Status:   Published
  Journal: International Journal of Biological Macromolecules
  Vol.:  214
  Year:  2022
  Pages:   642-654
  Supported by:  IPM
Increasing the temperature by just a few degrees may lead to structural perturbation or unfolding of the protein and consequent loss of function. The concepts of flexibility and rigidity are fundamental for understanding the relationships between function, structure and stability. Protein unfolding can often be triggered by thermal fluctuations with flexible residues usually on the protein surface. Therefore, identification and knowledge of the effect of modification to flexible regions in protein structures are required for efficient protein engineering and the rational design of thermally stable proteins. The most flexible regions in protein are loops, hence their rigidification is one of the effective strategies for increasing thermal stability. Directed evolution or rational design by computational prediction can also lead to the generation of thermally stable proteins. Computational protein design has been improved significantly in recent years and has successfully produced de novo stable backbone structures with optimized sequences and functions. This review discusses intramolecular and intermolecular interactions that determine the protein structure, and the strategies utilized in the mutagenesis of mesophilic proteins to stabilize and improve the functional characteristics of biocatalysts by describing efficient techniques and strategies to rigidify flexible loops at appropriate positions in the structure of the protein.

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