High thermodynamic stability of parametrically designed helical bundles
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High thermodynamic stability of parametrically designed helical bundles. / Huang, Po Ssu; Oberdorfer, Gustav; Xu, Chunfu; Pei, Xue Y.; Nannenga, Brent L.; Rogers, Joseph M.; DiMaio, Frank; Gonen, Tamir; Luisi, Ben; Baker, David.
In: Science, Vol. 346, No. 6208, 24.10.2014, p. 481-485.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
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
PY - 2014/10/24
Y1 - 2014/10/24
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.
UR - http://www.scopus.com/inward/record.url?scp=84908235298&partnerID=8YFLogxK
U2 - 10.1126/science.1257481
DO - 10.1126/science.1257481
M3 - Journal article
C2 - 25342806
AN - SCOPUS:84908235298
VL - 346
SP - 481
EP - 485
JO - Science
JF - Science
SN - 0036-8075
IS - 6208
ER -
ID: 244651037