Posfai, A., Zhou, J., Plotkin, J. B., Kinney, J. B., McCandlish, D. M. (August 2018) Selection for Protein Stability Enriches for Epistatic Interactions. Genes (Basel), 9 (9). ISSN 2073-4425 (Print)2073-4425
Abstract
A now classical argument for the marginal thermodynamic stability of proteins explains the distribution of observed protein stabilities as a consequence of an entropic pull in protein sequence space. In particular, most sequences that are sufficiently stable to fold will have stabilities near the folding threshold. Here, we extend this argument to consider its predictions for epistatic interactions for the effects of mutations on the free energy of folding. Although there is abundant evidence to indicate that the effects of mutations on the free energy of folding are nearly additive and conserved over evolutionary time, we show that these observations are compatible with the hypothesis that a non-additive contribution to the folding free energy is essential for observed proteins to maintain their native structure. In particular, through both simulations and analytical results, we show that even very small departures from additivity are sufficient to drive this effect.
| Item Type: | Paper |
|---|---|
| Subjects: | bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification |
| CSHL Authors: | |
| Communities: | CSHL labs > Kinney lab CSHL labs > McCandlish lab CSHL Cancer Center Program > Cancer Genetics and Genomics Program CSHL Cancer Center Program > Gene Regulation and Inheritance Program |
| Depositing User: | Matthew Dunn |
| Date: | 21 August 2018 |
| Date Deposited: | 30 Aug 2018 14:42 |
| Last Modified: | 26 Oct 2020 20:34 |
| PMCID: | PMC6162820 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/37163 |
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