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Computational protein design with electrostatic focusing : experimental characterization of a conditionally folded helical domain with a reduced amino acid alphabet
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Suárez-Diez, Maria, Pujol, Anaïs M., Matzapetakis, Manolis, Jaramillo, Alfonso and Iranzo, Olga (2013) Computational protein design with electrostatic focusing : experimental characterization of a conditionally folded helical domain with a reduced amino acid alphabet. Biotechnology Journal, 8 (7). pp. 855-864. doi:10.1002/biot.201200380 ISSN 18606768.
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Official URL: http://dx.doi.org/10.1002/biot.201200380
Abstract
Automated methodologies to design synthetic proteins from first principles use energy computations to estimate the ability of the sequences to adopt a targeted structure. This approach is still far from systematically producing native-like sequences, due, most likely, to inaccuracies when modeling the interactions between the protein and its aqueous environment. This is particularly challenging when engineering small protein domains (with less polar pair interactions than with the solvent). We have re-designed a three-helix bundle, domain B, using a fixed backbone and a four amino acid alphabet. We have enlarged the rotamer library with conformers that increase the weight of electrostatic interactions within the design process without altering the energy function used to compute the folding free energy. Our synthetic sequences show less than 15% similarity to any Swissprot sequence. We have characterized our sequences in different solvents using circular dichroism and nuclear magnetic resonance. The targeted structure achieved is dependent on the solvent used. This method can be readily extended to larger domains. Our method will be useful for the engineering of proteins that become active only in a given solvent and for designing proteins in the context of hydrophobic solvents, an important fraction of the situations in the cell.
Item Type: | Journal Article | ||||||||||
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Subjects: | T Technology > TP Chemical technology | ||||||||||
Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||||||||
Library of Congress Subject Headings (LCSH): | Protein engineering | ||||||||||
Journal or Publication Title: | Biotechnology Journal | ||||||||||
Publisher: | Wiley-Blackwell Publishing Ltd. | ||||||||||
ISSN: | 18606768 | ||||||||||
Official Date: | July 2013 | ||||||||||
Dates: |
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Volume: | 8 | ||||||||||
Number: | 7 | ||||||||||
Number of Pages: | 10 | ||||||||||
Page Range: | pp. 855-864 | ||||||||||
DOI: | 10.1002/biot.201200380 | ||||||||||
Status: | Peer Reviewed | ||||||||||
Publication Status: | Published | ||||||||||
Access rights to Published version: | Restricted or Subscription Access |
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