High thermodynamic stability of parametrically designed helical bundles

Po Ssu Huang, Gustav Oberdorfer, Chunfu Xu, Xue Y. Pei, Brent L. Nannenga, Joseph M. Rogers, Frank DiMaio, Tamir Gonen, Ben Luisi, David Baker

Research output: Contribution to journalArticle

135 Scopus citations

Abstract

We describe a procedure for designing proteins with backbones produced by varying the parameters in the Crick coiled coil-generating equations. Combinatorial design calculations identify low-energy sequences for alternative helix supercoil arrangements, and the helices in the lowest-energy arrangements are connected by loop building. We design an antiparallel monomeric untwisted three-helix bundle with 80-residue helices, an antiparallel monomeric right-handed four-helix bundle, and a pentameric parallel left-handed five-helix bundle. The designed proteins are extremely stable (extrapolated ΔGfold > 60 kilocalories per mole), and their crystal structures are close to those of the design models with nearly identical core packing between the helices. The approach enables the custom design of hyperstable proteins with fine-tuned geometries for a wide range of applications.

Original languageEnglish (US)
Pages (from-to)481-485
Number of pages5
JournalScience
Volume346
Issue number6208
DOIs
StatePublished - Oct 24 2014

ASJC Scopus subject areas

  • General

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    Huang, P. S., Oberdorfer, G., Xu, C., Pei, X. Y., Nannenga, B. L., Rogers, J. M., DiMaio, F., Gonen, T., Luisi, B., & Baker, D. (2014). High thermodynamic stability of parametrically designed helical bundles. Science, 346(6208), 481-485. https://doi.org/10.1126/science.1257481