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Updated: Jul 13, 2026
10:58
Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules
Published on: July 25, 2013
RETRACTED: Computational design of a biologically active enzyme
Mary A Dwyer1, Loren L Looger, Homme W Hellinga
1Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA.
Science (New York, N.Y.)
|June 26, 2004
Summary
Computational enzyme design successfully introduced triose phosphate isomerase activity into a non-enzymatic protein using 18-22 mutations. The engineered enzymes show significant rate enhancements and biological activity, supporting bacterial growth.
Area of Science:
- Protein chemistry
- Enzyme engineering
- Computational biology
Background:
- Enzyme activity is crucial for biological processes.
- Rational enzyme design is a challenging but important field.
- Understanding protein structure-function relationships is key.
Purpose of the Study:
- To computationally design and experimentally validate enzyme activity in a protein lacking it.
- To introduce triose phosphate isomerase (TIM) activity into ribose-binding protein (RBP).
- To demonstrate the generality of the computational design approach.
Main Methods:
- Utilized computational methods to predict mutations for introducing TIM activity into RBP.
- Designed proteins with 18 to 22 specific mutations.
- Experimentally validated the designed enzymes' activity and biological function.
Main Results:
- The designed proteins exhibited 10^5- to 10^6-fold rate enhancements compared to the uncatalyzed reaction.
- The engineered enzymes demonstrated biological activity, supporting Escherichia coli growth under gluconeogenic conditions.
- Successfully introduced a new enzymatic function into a non-enzymatic protein scaffold.
Conclusions:
- The computational design approach is effective for creating novel enzyme activities.
- This method has broad potential for designing a wide range of enzymes.
- The study validates the power of rational protein design in synthetic biology.
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