dorsal/arxiv
View SchemaStability and the Evolvability of Function in a Model Protein
| Authors | Jesse D Bloom, Claus O Wilke, Frances H Arnold, Christoph Adami |
|---|---|
| Categories | |
| ArXiv ID | q-bio/0401038 |
| URL | https://arxiv.org/abs/q-bio/0401038 |
| DOI | 10.1016/S0006-3495(04)74329-5 |
| Journal | Biophysical Journal, 86:2758-2764 (2004) |
Abstract
Functional proteins must fold with some minimal stability to a structure that can perform a biochemical task. Here we use a simple model to investigate the relationship between the stability requirement and the capacity of a protein to evolve the function of binding to a ligand. Although our model contains no built-in tradeoff between stability and function, proteins evolved function more efficiently when the stability requirement was relaxed. Proteins with both high stability and high function evolved more efficiently when the stability requirement was gradually increased than when there was constant selection for high stability. These results show that in our model, the evolution of function is enhanced by allowing proteins to explore sequences corresponding to marginally stable structures, and that it is easier to improve stability while maintaining high function than to improve function while maintaining high stability. Our model also demonstrates that even in the absence of a fundamental biophysical tradeoff between stability and function, the speed with which function can evolve is limited by the stability requirement imposed on the protein.
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"abstract": "Functional proteins must fold with some minimal stability to a structure that\ncan perform a biochemical task. Here we use a simple model to investigate the\nrelationship between the stability requirement and the capacity of a protein to\nevolve the function of binding to a ligand. Although our model contains no\nbuilt-in tradeoff between stability and function, proteins evolved function\nmore efficiently when the stability requirement was relaxed. Proteins with both\nhigh stability and high function evolved more efficiently when the stability\nrequirement was gradually increased than when there was constant selection for\nhigh stability. These results show that in our model, the evolution of function\nis enhanced by allowing proteins to explore sequences corresponding to\nmarginally stable structures, and that it is easier to improve stability while\nmaintaining high function than to improve function while maintaining high\nstability. Our model also demonstrates that even in the absence of a\nfundamental biophysical tradeoff between stability and function, the speed with\nwhich function can evolve is limited by the stability requirement imposed on\nthe protein.",
"arxiv_id": "q-bio/0401038",
"authors": [
"Jesse D Bloom",
"Claus O Wilke",
"Frances H Arnold",
"Christoph Adami"
],
"categories": [
"q-bio.BM"
],
"doi": "10.1016/S0006-3495(04)74329-5",
"journal_ref": "Biophysical Journal, 86:2758-2764 (2004)",
"title": "Stability and the Evolvability of Function in a Model Protein",
"url": "https://arxiv.org/abs/q-bio/0401038"
},
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