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 language | English |
---|---|
Pages (from-to) | 1737–1745 |
Number of pages | 9 |
Journal | Biochemical Society Transactions |
Volume | 52 |
Issue number | 4 |
Early online date | 3 Jul 2024 |
DOIs | |
Publication status | Published - 1 Aug 2024 |
Bibliographical note
© 2024 The Author(s).Structured keywords
- Bristol BioDesign Institute