Computational design of chemogenetic and optogenetic split proteins

Onur Dagliyan, Andrey Krokhotin, Irem Ozkan-Dagliyan, Alexander Deiters, Channing J. Der, Klaus M. Hahn, Nikolay V. Dokholyan

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Controlling protein activity with chemogenetics and optogenetics has proven to be powerful for testing hypotheses regarding protein function in rapid biological processes. Controlling proteins by splitting them and then rescuing their activity through inducible reassembly offers great potential to control diverse protein activities. Building split proteins has been difficult due to spontaneous assembly, difficulty in identifying appropriate split sites, and inefficient induction of effective reassembly. Here we present an automated approach to design effective split proteins regulated by a ligand or by light (SPELL). We develop a scoring function together with an engineered domain to enable reassembly of protein halves with high efficiency and with reduced spontaneous assembly. We demonstrate SPELL by applying it to proteins of various shapes and sizes in living cells. The SPELL server (spell.dokhlab.org) offers an automated prediction of split sites.

Original languageEnglish (US)
Article number4042
JournalNature communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Dagliyan, O., Krokhotin, A., Ozkan-Dagliyan, I., Deiters, A., Der, C. J., Hahn, K. M., & Dokholyan, N. V. (2018). Computational design of chemogenetic and optogenetic split proteins. Nature communications, 9(1), [4042]. https://doi.org/10.1038/s41467-018-06531-4