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Updated: Jun 27, 2025
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Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules
Published on: July 25, 2013
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Protein engineering using circular permutation - structure, function, stability, and applications.
Debanjana Das1, Sri Rama Koti Ainavarapu1
1Department of Chemical Sciences, Tata Institute of Fundamental Research, Mumbai, India.
The FEBS Journal
|April 27, 2024
Summary
Circular permutation (CP) engineers proteins by rearranging amino acid sequences, creating novel variants for diverse applications. Understanding CP
Area of Science:
- Protein Engineering
- Biochemistry
- Structural Biology
Background:
- Protein engineering creates novel protein variants using methods like rational design and directed evolution.
- Expanding the amino acid repertoire with unnatural amino acids broadens possibilities.
- Circular permutation (CP) rearranges amino acid sequences to alter connectivity while preserving overall structure.
Purpose of the Study:
- To review techniques for creating circular permutation proteins (CPs).
- To explore the diverse biological applications of designed CPs.
- To discuss the impact of CP on protein thermodynamic and kinetic stability.
Main Methods:
- Review of existing literature on protein engineering techniques.
- Analysis of experimental and computational studies on CP proteins.
- Discussion of native chemical ligation and codon expansion for unnatural amino acids.
Main Results:
- CP proteins are utilized in biocatalysis, sensing, genome editing, and optogenetics.
- CP can alter protein stability and catalytic efficiency, but effects are not predictable a priori.
- Understanding CP's impact on the energy landscape is crucial for protein design.
Conclusions:
- CP is a powerful protein redesign strategy with broad applications.
- Further research is needed to predict and control CP's effects on protein stability.
- Designing robust CP proteins requires a comprehensive understanding of their structural and energetic properties.
Keywords:
artificial proteinscircular permutationcontact ordermechanical unfoldingprotein designprotein engineeringprotein foldingprotein sensorsMore Related Videos
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