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Structures and disulfide cross-linking of de novo designed therapeutic mini-proteins.

ABSTRACT: 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.

SUBMITTER: Silva DA

PROVIDER: S-EPMC6001749 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Structures and disulfide cross-linking of de novo designed therapeutic mini-proteins.

Silva Daniel-Adriano DA Stewart Lance L Lam Kwok-Ho KH Jin Rongsheng R Baker David D

The FEBS journal 20180306 10

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 In ...[more]

PMID: 29389072

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