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Cited by 251

The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.

De novo design of a four-fold symmetric TIM-barrel protein with atomic-level accuracy

Open access
Huang, Po-Ssu, Feldmeier, Kaspar, Parmeggiani, Fabio, Fernandez Velasco, D Alejandro, Höcker, Birte, Baker, David·2016·Nature Chemical Biology

Abstract

Despite efforts for over 25 years, de novo protein design has not succeeded in achieving the TIM-barrel fold. Here we describe the computational design of 4-fold symmetrical (β/α)8-barrels guided by geometrical and chemical principles. Experimental characterization of 33 designs revealed the importance of sidechain-backbone hydrogen bonding for defining the strand register between repeat units. The X-ray crystal structure of a designed thermostable 184-residue protein is nearly identical with the designed TIM-barrel model. PSI-BLAST searches do not identify sequence similarities to known TIM-barrel proteins, and sensitive profile-profile searches indicate that the design sequence is distant from other naturally occurring TIM-barrel superfamilies, suggesting that Nature has only sampled a subset of the sequence space available to the TIM-barrel fold. The ability to de novo design TIM-barrels opens new possibilities for custom-made enzymes.

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Crossref · 10.1038/nchembio.1966

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Metadata

Authors
Huang, P.-S., Feldmeier, K., Parmeggiani, F., Fernandez Velasco, D. A., Höcker, B., & Baker, D.
Venue
Nature Chemical Biology
Published
2015-11-23
Volume
12
Issue
1
Pages
29-34
ISSN
  • 1552-4450 (ISSN-L)
  • 1552-4469
OpenAlex
W2173280871
Cited by
251
References
8
FWCI
9.26
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: De novo design of a four-fold symmetric TIM-barrel protein with atomic-level accuracy. https://app.cochat.ai/papers/10.1038/nchembio.1966
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Huang, P.-S., Feldmeier, K., Parmeggiani, F., Fernandez Velasco, D. A., Höcker, B., & Baker, D. (2016). De novo design of a four-fold symmetric TIM-barrel protein with atomic-level accuracy. Nature Chemical Biology. https://doi.org/10.1038/nchembio.1966

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