title: The CamSol method of rational design of protein mutants with enhanced solubility.
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.
authors.affiliation: Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK.
authors.forename: Pietro
authors.initials: P
authors.lastname: Sormanni
authors.affiliation: Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK.
authors.forename: Francesco A
authors.initials: FA
authors.lastname: Aprile
authors.affiliation: Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK. Electronic address: mv245@cam.ac.uk.
authors.forename: Michele
authors.initials: M
authors.lastname: Vendruscolo
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D055598:Chemical Phenomena; D002942:Circular Dichroism; D003001:Cloning, Molecular; D003198:Computer Simulation; D004926:Escherichia coli / Q000235:genetics; D008958:Models, Molecular; D015394:Molecular Structure; D050505:Mutant Proteins / Q000737:chemistry* / Q000235:genetics*; D011487:Protein Conformation; D015202:Protein Engineering / Q000379:methods*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D012995:Solubility
chemical_list: D000596:Amino Acids; D050505:Mutant Proteins; D011994:Recombinant Proteins
keywords: protein aggregation; protein solubility