Selection for Protein Stability Enriches for Epistatic Interactions

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

URL: https://www.ncbi.nlm.nih.gov/pubmed/30134605
DOI: 10.3390/genes9090423

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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