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Updated: May 25, 2026

Synthesizing Amino Acids Modified with Reactive Carbonyls in Silico to Assess Structural Effects Using Molecular Dynamics Simulations
Published on: April 26, 2024
Increased Diels-Alderase activity through backbone remodeling guided by Foldit players
Christopher B Eiben1, Justin B Siegel, Jacob B Bale
1Department of Biochemistry, University of Washington, Seattle, Washington, USA.
Crowdsourcing via the Foldit game enhanced a computationally designed enzyme
Area of Science:
- Biochemistry
- Computational Biology
- Biotechnology
Background:
- De novo enzyme design creates catalysts but with lower efficiency than natural enzymes.
- Computational enzyme design is crucial for developing renewable fuels, drugs, and chemicals.
Purpose of the Study:
- To enhance the catalytic activity of a computationally designed enzyme.
- To explore game-driven crowdsourcing for enzyme structure and function remodeling.
Main Methods:
- Utilized the online game Foldit for enzyme redesign.
- Challenged players to remodel the backbone of a designed Diels-Alderase enzyme.
- Iterative design, characterization, and X-ray crystallography were employed.
Main Results:
- A 24-residue helix-turn-helix motif, including a 13-residue insertion, was generated.
- Enzyme activity increased more than 18-fold.
- X-ray crystallography confirmed the modeled structure of the insertion.
Conclusions:
- Human creativity can be leveraged for molecular-scale design.
- Game-driven crowdsourcing is effective for improving enzyme function.
- This approach advances computational enzyme design capabilities.
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