How Protein Stability and New Functions Trade Off
Author Information
Author(s): Tokuriki Nobuhiko, Stricher Francois, Serrano Luis, Tawfik Dan S.
Primary Institution: Weizmann Institute of Science, Rehovot, Israel
Hypothesis
How are the destabilizing effects of functional mutations balanced to enable adaptation?
Conclusion
The evolution of new enzymatic activities depends on the compensatory, stabilizing effect of apparently 'silent' mutations in regions of the protein that are irrelevant to its function.
Supporting Evidence
- Mutations that modulate enzymatic functions are mostly destabilizing.
- Many mutations that appear in directed evolution variants with no obvious role in the new function exert stabilizing effects.
- New-function mutations are distributed similarly to all other mutations.
Takeaway
When proteins change to do new jobs, they often become less stable, but some other changes help keep them stable.
Methodology
ΔΔG computations by FoldX were applied to analyze the effects of 548 mutations from directed evolution of 22 different enzymes.
Limitations
The FoldX values are predictions of limited accuracy.
Digital Object Identifier (DOI)
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