Computational design of de novo bioenergetic membrane proteins

Benjamin J Hardy, Paul Curnow*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

Abstract

The major energy-producing reactions of biochemistry occur at biological membranes. Computational protein design now provides the opportunity to elucidate the underlying principles of these processes and to construct bioenergetic pathways on our own terms. Here, we review recent achievements in this endeavour of 'synthetic bioenergetics', with a particular focus on new enabling tools that facilitate the computational design of biocompatible de novo integral membrane proteins. We use recent examples to showcase some of the key computational approaches in current use and highlight that the overall philosophy of 'surface-swapping' - the replacement of solvent-facing residues with amino acids bearing lipid-soluble hydrophobic sidechains - is a promising avenue in membrane protein design. We conclude by highlighting outstanding design challenges and the emerging role of AI in sequence design and structure ideation.
Original languageEnglish
Pages (from-to)1737–1745
Number of pages9
JournalBiochemical Society Transactions
Volume52
Issue number4
Early online date3 Jul 2024
DOIs
Publication statusPublished - 1 Aug 2024

Bibliographical note

© 2024 The Author(s).

Structured keywords

  • Bristol BioDesign Institute

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