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Stability and the Evolvability of Function in a Model Protein

Bloom, Jesse D. and Wilke, Claus O. and Arnold, Frances H. and Adami, Christoph (2004) Stability and the Evolvability of Function in a Model Protein. Biophysical Journal, 86 (5). pp. 2758-2764. ISSN 0006-3495. PMCID PMC1304146. doi:10.1016/S0006-3495(04)74329-5. https://resolver.caltech.edu/CaltechAUTHORS:20180823-073709439

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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.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1016/S0006-3495(04)74329-5DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1304146PubMed CentralArticle
ORCID:
AuthorORCID
Bloom, Jesse D.0000-0003-1267-3408
Wilke, Claus O.0000-0002-7470-9261
Arnold, Frances H.0000-0002-4027-364X
Adami, Christoph0000-0002-2915-9504
Additional Information:© 2004 The Biophysical Society. Published by Elsevier Inc. Under an Elsevier user license. Received 7 November 2003, Accepted 12 January 2004, Available online 6 January 2009. We thank Hue Sun Chan, George Somero, Jeff Endelman, and Chris Voigt for their helpful comments on the manuscript. J.D.B. is supported by a Howard Hughes Medical Institute predoctoral fellowship. C.O.W. and C.A. were supported by the National Science Foundation under contract No. DEB-9981397. Part of this work was carried out at the Jet Propulsion Laboratory, California Institute of Technology, under a contract with the National Aeronautics and Space Administration.
Funders:
Funding AgencyGrant Number
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
NSFDEB-9981397
NASA/JPL/CaltechUNSPECIFIED
Issue or Number:5
PubMed Central ID:PMC1304146
DOI:10.1016/S0006-3495(04)74329-5
Record Number:CaltechAUTHORS:20180823-073709439
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20180823-073709439
Official Citation:Jesse D. Bloom, Claus O. Wilke, Frances H. Arnold, Christoph Adami, Stability and the Evolvability of Function in a Model Protein, Biophysical Journal, Volume 86, Issue 5, 2004, Pages 2758-2764, ISSN 0006-3495, https://doi.org/10.1016/S0006-3495(04)74329-5. (http://www.sciencedirect.com/science/article/pii/S0006349504743295)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:89072
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:23 Aug 2018 16:52
Last Modified:16 Nov 2021 00:32

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