Computational design of water-soluble  -helical barrels

DOI: 10.1126/science.1257452
PMID: 25342807

Authors: Andrew Thomson (University of Bristol) , C. W. Wood (University of Bristol) , Antony Burton (University of Bristol) , Gail Bartlett (University of Bristol) , R. B. Sessions (University of Bristol) , Leo Brady (University of Bristol) , D. N. Woolfson (University of Bristol)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Science , VOL 346 (6208) , PAGES 485 - 488

State: Published (Approved)
Published: October 2014
Diamond Proposal Number(s): 8922

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.

Journal Keywords: Models ; Molecular ; Peptides ; Protein; Secondary ; Solubility ; Water

Subject Areas: Biology and Bio-materials


Instruments: I03-Macromolecular Crystallography , I04-Macromolecular Crystallography

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