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J Mol Biol. 2015 Jan 30;427(2):478-90. doi: 10.1016/j.jmb.2014.09.026. Epub 2014 Oct 14.

The CamSol method of rational design of protein mutants with enhanced solubility.

Author information

1
Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK.
2
Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK. Electronic address: mv245@cam.ac.uk.

Abstract

Protein solubility is often an essential requirement in biotechnological and biomedical applications. Great advances in understanding the principles that determine this specific property of proteins have been made during the past decade, in particular concerning the physicochemical characteristics of their constituent amino acids. By exploiting these advances, we present the CamSol method for the rational design of protein variants with enhanced solubility. The method works by performing a rapid computational screening of tens of thousand of mutations to identify those with the greatest impact on the solubility of the target protein while maintaining its native state and biological activity. The application to a single-domain antibody that targets the Alzheimer's Aβ peptide demonstrates that the method predicts with great accuracy solubility changes upon mutation, thus offering a cost-effective strategy to help the production of soluble proteins for academic and industrial purposes.

KEYWORDS:

protein aggregation; protein solubility

PMID:
25451785
DOI:
10.1016/j.jmb.2014.09.026
[Indexed for MEDLINE]

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