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Updated: Sep 16, 2025
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Spatiotemporal Control of Protein Activity through Optogenetic Allosteric Regulation
Published on: October 4, 2024
697
Epistasis in Allosteric Proteins: Can Biophysical Models Provide a Better Framework for Prediction and Understanding?
David Ross1, Drew S Tack1, Peter D Tonner1
1National Institute of Standards and Technology, Gaithersburg, MD 20899, USA.
Journal of Molecular Biology
|July 5, 2025
Summary
Predicting mutation interactions (epistasis) in allosteric proteins like LacI is challenging. Biophysical models offer a more parsimonious explanation of epistasis compared to phenomenological models.
Area of Science:
- Protein science
- Biophysics
- Biotechnology
Background:
- Epistasis, or mutation interaction, is crucial in protein science but complex to predict.
- Allosteric proteins present additional challenges due to intricate conformational states and binding networks.
Purpose of the Study:
- To compare biophysical and phenomenological models for analyzing mutational effects and epistasis.
- To investigate these models using the lac repressor protein (LacI).
Main Methods:
- Systematic comparison of biophysical and phenomenological models.
- Analysis of an extensive dataset of 164 LacI variants' dose-response measurements.
Main Results:
- The phenomenological Hill model showed slightly higher predictive accuracy.
- The biophysical model provided a more parsimonious fit with significantly less epistasis.
- LacI variants data was used to compare models.
Conclusions:
- Allosteric function is inherently multi-state and multi-dimensional.
- Biophysical models may offer benefits for analyzing mutational effects and epistasis in allosteric proteins.
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