Cited by 331Protein Structure and DynamicsChemical Synthesis and AnalysisEnzyme Structure and Function

Computational design of water-soluble α-helical barrels

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Thomson, Andrew R., Wood, Christopher W., Burton, Antony J., Bartlett, Gail J., Sessions, Richard B., Brady, R. Leo, Woolfson, Derek N.·2014·Science

Abstract

The design of protein sequences that fold into prescribed de novo structures is challenging. General solutions to this problem require geometric descriptions of protein folds and methods to fit sequences to these. The α-helical coiled coils present a promising class of protein for this and offer considerable scope for exploring hitherto unseen structures. For α-helical barrels, which have more than four helices and accessible central channels, many of the possible structures remain unobserved. Here, we combine geometrical considerations, knowledge-based scoring, and atomistic modeling to facilitate the design of new channel-containing α-helical barrels. X-ray crystal structures of the resulting designs match predicted in silico models. Furthermore, the observed channels are chemically defined and have diameters related to oligomer state, which present routes to design protein function.

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Crossref · 10.1126/science.1257452

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Authors
Thomson, A. R., Wood, C. W., Burton, A. J., Bartlett, G. J., Sessions, R. B., Brady, R. L., & Woolfson, D. N.
Affiliations
University of Bristol (GB)
Corresponding author
  • Thomson, Andrew R.
  • Wood, Christopher W.
  • Burton, Antony J.
  • Woolfson, Derek N.
Venue
Science
Published
2014-10-24
Volume
346
Issue
6208
Pages
485-488
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W1834588461
Cited by
330
References
40
Citations by year
2026: 11 · 2025: 19 · 2024: 21 · 2023: 17 · 2022: 30 · 2021: 35 · 2020: 35 · 2019: 36 · 2018: 27 · 2017: 41 · 2016: 41 · 2015: 14 · 2014: 3
FWCI
13.54
Type
journal article
Language
en
Licence
other-oa
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • Bristol Research (University of Bristol) (submittedVersion, other-oa)
Funders
  • Engineering and Physical Sciences Research Council (EP/K03927X/1, EP/J001430/1, 1115150)
  • Biotechnology and Biological Sciences Research Council (BB/L01386X/1, BB/J008990/1, 1228976)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chemical Synthesis and Analysis
  • Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
Keywords
de novo protein design, coiled coil, protein folding, knowledge-based scoring, water-soluble proteins, protein oligomerization, atomistic modeling
MeSH terms
Models, Molecular, Peptides, Solubility, Water, Protein Structure, Secondary, Computational Biology

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