Computational design of water-soluble α-helical barrels

Thomson, A. R. , Wood, C. W., Burton, A. J., Bartlett, G. J., Sessions, R. B., Brady, R. L. and Woolfson, D. N. (2014) Computational design of water-soluble α-helical barrels. Science, 346(6208), pp. 485-488. (doi:10.1126/science.1257452) (PMID:25342807)

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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.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Thomson, Dr Drew
Authors: Thomson, A. R., Wood, C. W., Burton, A. J., Bartlett, G. J., Sessions, R. B., Brady, R. L., and Woolfson, D. N.
College/School:College of Science and Engineering > School of Chemistry
Journal Name:Science
Publisher:American Association for the Advancement of Science
ISSN (Online):1095-9203

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