Native state of natural proteins optimizes local entropy
M Negri1, G Tiana2, R Zecchina3
1Department Applied Science and Technology, Politecnico di Torino, CorsoDuca degli Abruzzi 24, I-10129 Turin, Italy.
Physical Review. E
|January 15, 2022
Summary
Local entropy effectively describes the native state of proteins, enhancing protein stability and folding rates. This finding offers a new physical concept for understanding protein folding dynamics.
Area of Science:
- Computational Biology
- Biophysics
- Statistical Mechanics
Background:
- Protein native states are traditionally explained by kinetic accessibility or thermodynamic stability.
- Physical concepts and sampling algorithms, including artificial neural networks, have advanced disordered system studies.
Purpose of the Study:
- To quantitatively explore the utility of local entropy in describing the native state of model proteins.
- To investigate if local entropy can predict or enhance protein stability and folding rates.
Main Methods:
- Utilized physical concepts and sampling algorithms from disordered systems research.
- Applied artificial neural networks for efficient sampling of protein conformations.
- Investigated local entropy in both lattice models and all-atom protein representations.
Main Results:
- Demonstrated efficient sampling of high local entropy states in model proteins.
- Provided proof of concept for enhanced protein stability linked to local entropy.
- Showcased accelerated protein folding rates associated with high local entropy.
Conclusions:
- Local entropy is a valuable descriptor for the native state of proteins.
- The developed methods, based on statistical mechanics, are broadly applicable.
- This approach offers a new perspective on protein folding and stability.
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