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Updated: Sep 23, 2025
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Application of I TASSER, trRosetta, UCSF Chimera, HADDOCK server, and HEX loria for De Novo and In Silico Design of Proteins
Published on: July 8, 2025
393
Design and discovery of metamorphic proteins
Acacia F Dishman1, Brian F Volkman2
1Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI, USA; Medical Scientist Training Program, Medical College of Wisconsin, Milwaukee, WI, USA.
Current Opinion in Structural Biology
|May 13, 2022
Summary
Metamorphic proteins are unique sequences that switch between multiple structures with distinct functions. Discovering new metamorphic proteins aids disease therapies and designing novel protein-based applications.
Area of Science:
- Biochemistry
- Structural Biology
- Protein Engineering
Background:
- Metamorphic proteins reversibly interconvert between distinct native structures and functions.
- An estimated 4% of Protein Data Bank (PDB) entries may represent metamorphic proteins.
- Common features include marginal thermostability and variable predicted secondary structures.
Purpose of the Study:
- To highlight the significance of metamorphic proteins in biology and medicine.
- To discuss challenges and opportunities in identifying and designing fold-switching proteins.
- To explore the therapeutic and biotechnological potential of metamorphic proteins.
Main Methods:
- Literature review and analysis of existing metamorphic protein data.
- Identification of common biophysical characteristics of metamorphic proteins.
- Exploration of potential applications based on fold-switching capabilities.
Main Results:
- Several metamorphic proteins have been identified since the early 2000s.
- Metamorphic proteins exhibit unique structural plasticity and functional divergence.
- Challenges remain in identifying novel natural metamorphic proteins and designing artificial ones.
Conclusions:
- Identifying new metamorphic proteins can improve targeting of disease-related proteins and enhance protein-based therapies.
- Designed fold-switching proteins offer diverse applications, including biosensors, molecular switches, and self-assembling systems.
- Further research into metamorphic proteins is crucial for advancing medicine and biotechnology.
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