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Published on: February 11, 2019
A molecular mechanism for osmolyte-induced protein stability
Timothy O Street1, D Wayne Bolen, George D Rose
1T. C. Jenkins Department of Biophysics, The Johns Hopkins University, Jenkins Hall, 3400 North Charles Street, Baltimore, MD 21218, USA.
Summary
Protecting osmolytes stabilize proteins by interacting favorably with the protein backbone. A new model explains how osmolyte properties predict their effect on protein stability and folding.
Area of Science:
- Biochemistry
- Chemical Physics
Background:
- Osmolytes are vital organic compounds influencing protein stability.
- Existing theories lack a universal explanation for osmolyte-protein interactions.
- Osmolytes can either stabilize (protecting) or destabilize (denaturing) proteins.
Purpose of the Study:
- To develop a universal molecular theory for osmolyte-induced protein stability changes.
- To establish a quantitative model for osmolyte-protein interactions.
- To correlate osmolyte properties with their effects on protein folding equilibrium.
Main Methods:
- Analysis of the transfer free energy (Deltagtr) of protein backbones in osmolyte solutions.
- Development of a quantitative solvation model based on interactant polarity and surface area.
- Correlation of calculated Deltagtr values with experimental data.
Main Results:
- A negative correlation was found between Deltagtr and osmolyte fractional polar surface area.
- The developed solvation model accurately predicted Deltagtr values (R = 0.99).
- The model correctly predicted preferential exclusion/accumulation of osmolytes around the protein backbone.
Conclusions:
- Osmolyte interactions with protein backbones are governed by polarity and surface area.
- The model provides a universal mechanism for understanding osmolyte effects on protein stability.
- This work rationalizes experimental observations in protein stabilization and denaturation studies.
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