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Structures and disulfide cross‐linking of de novo designed therapeutic mini‐proteins
Author(s) -
Silva DanielAdriano,
Stewart Lance,
Lam KwokHo,
Jin Rongsheng,
Baker David
Publication year - 2018
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.14394
Subject(s) - disulfide bond , folding (dsp implementation) , computational biology , protein design , computer science , pipeline (software) , protein folding , hemagglutinin (influenza) , chemistry , protein structure , biochemistry , biology , engineering , programming language , gene , electrical engineering
Recent advances in computational protein design now enable the massively parallel de novo design and experimental characterization of small hyperstable binding proteins with potential therapeutic activity. By providing experimental feedback on tens of thousands of designed proteins, the design‐build‐test‐learn pipeline provides a unique opportunity to systematically improve our understanding of protein folding and binding. Here, we review the structures of mini‐protein binders in complex with Influenza hemagglutinin and Bot toxin, and illustrate in the case of disulfide bond placement how analysis of the large datasets of computational models and experimental data can be used to identify determinants of folding and binding.