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
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.
10.1126/science.1257481
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Thermodynamics Medicine & Life Sciences 100%
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
High thermodynamic stability of parametrically designed helical bundles. / Huang, Po Ssu; Oberdorfer, Gustav; Xu, Chunfu et al.
In: Science, Vol. 346, No. 6208, 24.10.2014, p. 481-485.
Huang, PS, Oberdorfer, G, Xu, C, Pei, XY, Nannenga, BL, Rogers, JM, DiMaio, F, Gonen, T, Luisi, B & Baker, D 2014, 'High thermodynamic stability of parametrically designed helical bundles', Science, vol. 346, no. 6208, pp. 481-485. https://doi.org/10.1126/science.1257481
Huang PS, Oberdorfer G, Xu C, Pei XY, Nannenga BL, Rogers JM et al. High thermodynamic stability of parametrically designed helical bundles. Science. 2014 Oct 24;346(6208):481-485. doi: 10.1126/science.1257481
Huang, Po Ssu ; Oberdorfer, Gustav ; Xu, Chunfu et al. / High thermodynamic stability of parametrically designed helical bundles. In: Science. 2014 ; Vol. 346, No. 6208. pp. 481-485.
@article{9149399f6fbb4f659ceffe040a88b533,
title = "High thermodynamic stability of parametrically designed helical bundles",
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.",
author = "Huang, {Po Ssu} and Gustav Oberdorfer and Chunfu Xu and Pei, {Xue Y.} and Nannenga, {Brent L.} and Rogers, {Joseph M.} and Frank DiMaio and Tamir Gonen and Ben Luisi and David Baker",
note = "Publisher Copyright: {\textcopyright} 2014, American Association for the Advancement of Science. All rights reserved.",
doi = "10.1126/science.1257481",
journal = "Science",
publisher = "American Association for the Advancement of Science",
T1 - High thermodynamic stability of parametrically designed helical bundles
AU - Huang, Po Ssu
AU - Oberdorfer, Gustav
AU - Xu, Chunfu
AU - Pei, Xue Y.
AU - Nannenga, Brent L.
AU - Rogers, Joseph M.
AU - DiMaio, Frank
AU - Gonen, Tamir
AU - Luisi, Ben
AU - Baker, David
N1 - Publisher Copyright: © 2014, American Association for the Advancement of Science. All rights reserved.
N2 - 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.
AB - 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.
U2 - 10.1126/science.1257481
DO - 10.1126/science.1257481
JO - Science
JF - Science