title: Designability landscape reveals sequence features that define axial helix rotation in four-helical homo-oligomeric antiparallel coiled-coil structures.
abstract: Coiled coils are widespread protein domains comprising α-helices wound around each other in a regular fashion. Owing to their regularity, coiled-coil structures can be fully described by parametric equations. This in turn makes them an excellent model for studying sequence-structure relationships in proteins. Here, we used computational design to identify sequence features that determine the degree of helix axial rotation in four-helical homo-oligomeric antiparallel coiled coils. We designed 135,000 artificial sequences for a repertoire of backbone models representing all theoretically possible axial rotation states. Analysis of the designed sequences revealed features that precisely define the rotation of the helices. Based on these features we implemented a bioinformatic tool, which given a coiled-coil sequence, predicts the rotation of the helices in its structure. Moreover, we showed that another structural parameter, helix axial shift, is coupled to helix axial rotation and that dependence between these two parameters narrows the number of possible axial rotation states.
authors.affiliation: International Institute of Molecular and Cell Biology in Warsaw, Laboratory of Bioinformatics and Protein Engineering, 4 Ks. Trojdena Street, 02-109 Warsaw, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Szczepaniak
authors.affiliation: International Institute of Molecular and Cell Biology in Warsaw, Laboratory of Bioinformatics and Protein Engineering, 4 Ks. Trojdena Street, 02-109 Warsaw, Poland.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Lach
authors.affiliation: International Institute of Molecular and Cell Biology in Warsaw, Laboratory of Bioinformatics and Protein Engineering, 4 Ks. Trojdena Street, 02-109 Warsaw, Poland; Bioinformatics Laboratory, Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz University, Poznań 61-614, Poland. Electronic address: iamb@genesilico.pl.
authors.forename: Janusz M
authors.initials: JM
authors.lastname: Bujnicki
authors.affiliation: International Institute of Molecular and Cell Biology in Warsaw, Laboratory of Bioinformatics and Protein Engineering, 4 Ks. Trojdena Street, 02-109 Warsaw, Poland. Electronic address: sdh@genesilico.pl.
authors.forename: Stanislaw
authors.initials: S
authors.lastname: Dunin-Horkawicz
mesh_terms: D000595:Amino Acid Sequence; D019295:Computational Biology / Q000379:methods; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry*; D012399:Rotation
chemical_list: D011506:Proteins
keywords: Bioinformatics; Coiled-coil domains; Protein design; Protein modeling; Sequence–structure relationship