Structure-based design of supercharged, highly thermoresistant antibodies

Aleksandr E. Miklos, Christien Kluwe, Bryan S. Der, Supriya Pai, Aroop Sircar, Randall A. Hughes, Monica Berrondo, Jianqing Xu, Vlad Codrea, Patricia E. Buckley, Alena M. Calm, Heather S. Welsh, Candice R. Warner, Melody A. Zacharko, James P. Carney, Jeffrey J. Gray, George Georgiou, Brian Kuhlman, Andrew D. Ellington

Research output: Contribution to journalArticlepeer-review

122 Scopus citations


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 ≈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.

Original languageEnglish (US)
Pages (from-to)449-455
Number of pages7
JournalChemistry and Biology
Issue number4
StatePublished - Apr 20 2012
Externally publishedYes

ASJC Scopus subject areas

  • Drug Discovery
  • Molecular Medicine
  • Molecular Biology
  • Biochemistry
  • Clinical Biochemistry
  • Pharmacology


Dive into the research topics of 'Structure-based design of supercharged, highly thermoresistant antibodies'. Together they form a unique fingerprint.

Cite this