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Updated: Dec 19, 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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Harnessing Conformational Plasticity to Generate Designer Enzymes.
Rory M Crean1, Jasmine M Gardner1, Shina C L Kamerlin1
1Department of Chemistry - BMC, Uppsala University, Box 576, 751 23 Uppsala, Sweden.
Journal of the American Chemical Society
|June 5, 2020
Summary
Understanding enzyme conformational dynamics is key for creating new enzymes and improving existing ones. Computational and laboratory methods can engineer these dynamics for novel biocatalyst design.
Area of Science:
- Biochemistry and Molecular Biology
- Computational Biology
- Protein Engineering
Background:
- Conformational dynamics play a crucial role in enzyme evolution and the emergence of new catalytic activities.
- Targeted engineering of conformational dynamics has shown success in modifying enzyme selectivity and activity.
- Current computational enzyme design often overlooks conformational flexibility, focusing on sequence or static structures.
Purpose of the Study:
- To provide an overview of evolutionary studies on the role of conformational dynamics in enzyme evolution.
- To highlight advances in computational approaches for targeting conformational dynamics in enzyme design.
- To emphasize harnessing conformational dynamics for engineering next-generation biocatalysts.
Main Methods:
- Review of evolutionary studies dissecting the role of conformational dynamics.
- Survey of computational approaches for incorporating conformational dynamics into enzyme design.
- Integration of computational methods with laboratory evolution and traditional design strategies.
Main Results:
- Evolutionary studies demonstrate the importance of conformational dynamics in novel enzyme emergence.
- Computational tools are increasingly available to target and engineer protein flexibility.
- Combining dynamics-focused design with experimental evolution expands the protein engineering toolkit.
Conclusions:
- Conformational dynamics are fundamental to enzyme function, evolution, and engineering.
- Computational approaches can effectively incorporate protein dynamics into enzyme design strategies.
- Harnessing conformational dynamics offers a powerful paradigm for developing designer biocatalysts.
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