title: Computational design of water-soluble α-helical barrels.
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.
authors.affiliation: School of Chemistry, University of Bristol, Cantock's Close, Bristol, BS8 1TS, UK. chzart@bristol.ac.uk d.n.woolfson@bristol.ac.uk.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Thomson
authors.affiliation: School of Chemistry, University of Bristol, Cantock's Close, Bristol, BS8 1TS, UK. School of Biochemistry, University of Bristol, Medical Sciences Building, University Walk, Bristol, BS8 1TD, UK.
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Wood
authors.affiliation: School of Chemistry, University of Bristol, Cantock's Close, Bristol, BS8 1TS, UK.
authors.forename: Antony J
authors.initials: AJ
authors.lastname: Burton
authors.affiliation: School of Chemistry, University of Bristol, Cantock's Close, Bristol, BS8 1TS, UK.
authors.forename: Gail J
authors.initials: GJ
authors.lastname: Bartlett
authors.affiliation: School of Biochemistry, University of Bristol, Medical Sciences Building, University Walk, Bristol, BS8 1TD, UK.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Sessions
authors.affiliation: School of Biochemistry, University of Bristol, Medical Sciences Building, University Walk, Bristol, BS8 1TD, UK.
authors.forename: R Leo
authors.initials: RL
authors.lastname: Brady
authors.affiliation: School of Chemistry, University of Bristol, Cantock's Close, Bristol, BS8 1TS, UK. School of Biochemistry, University of Bristol, Medical Sciences Building, University Walk, Bristol, BS8 1TD, UK. chzart@bristol.ac.uk d.n.woolfson@bristol.ac.uk.
authors.forename: Derek N
authors.initials: DN
authors.lastname: Woolfson
mesh_terms: D019295:Computational Biology; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry; D017433:Protein Structure, Secondary; D012995:Solubility; D014867:Water / Q000737:chemistry*
chemical_list: D010455:Peptides; D014867:Water