期刊
CHEMISTRY & BIOLOGY
卷 19, 期 4, 页码 449-455出版社
CELL PRESS
DOI: 10.1016/j.chembiol.2012.01.018
关键词
-
资金
- DARPA [HR-0011-10-1-0052]
Mutation of surface residues to charged amino acids increases resistance to aggregation and can enable reversible unfolding. We have developed a protocol using the Rosetta computational design package that supercharges proteins while considering the energetic implications of each mutation. Using a homology model, a single-chain variable fragment antibody was designed that has a markedly enhanced resistance to thermal inactivation and displays an unanticipated approximate to 30-fold improvement in affinity. Such supercharged antibodies should prove useful for assays in resource-limited settings and for developing reagents with improved shelf lives.
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