Computational redesign of the lipid-facing surface of the outer membrane protein OmpA

James A. Stapleton, Timothy A. Whitehead, Vikas Nanda

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


Advances in computational design methods have made possible extensive engineering of soluble proteins, but designed β-barrel membrane proteins await improvements in our understanding of the sequence determinants of folding and stability. A subset of the amino acid residues of membrane proteins interact with the cell membrane, and the design rules that govern this lipid-facing surface are poorly understood. We applied a residue-level depth potential for β-barrel membrane proteins to the complete redesign of the lipid-facing surface of Escherichia coli OmpA. Initial designs failed to fold correctly, but reversion of a small number of mutations indicated by backcross experiments yielded designs with substitutions to up to 60% of the surface that did support folding and membrane insertion.

Original languageEnglish (US)
Pages (from-to)9632-9637
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number31
StatePublished - Aug 4 2015

All Science Journal Classification (ASJC) codes

  • General


  • Membrane proteins
  • OmpA
  • Protein design
  • Statistical potential
  • β-barrel


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