title: Seven-helix bundles: molecular modeling via restrained molecular dynamics.
abstract: Simulated annealing via restrained molecular dynamics (SA/MD) has been used to model compact bundles of seven approximately (anti)parallel alpha-helices. Seven such helix bundles occur, e.g., in bacteriorhodopsin, in rhodopsin, and in the channel-forming N-terminal domain of Bacillus thuringiensis delta-endotoxin. Two classes of model are considered: (a) those consisting of seven Ala20 peptide chains; and (b) those containing a single polypeptide chain, made up of seven Ala20 helices linked by GlyN interhelix loops (where N = 5 or 10). Three different starting C alpha templates for SA/MD are used, in which the seven helices are arranged (a) on a left-handed circular template, (b) on a bacteriorhodopsin-like template, or (c) on a zig-zag template. The ensembles of models generated by SA/MD are analyzed in terms of their geometry and energetics, and the most stable structures from each ensemble are examined in greater detail. Structures resembling bacteriorhodopsin and structures resembling delta-endotoxin are both represented among the most stable structures. delta-Endotoxin-like structures arise from both circular and bacteriorhodopsin-like C alpha templates. A third helix-packing mode occurs several times among the stable structures, regardless of the C alpha template and of the presence or absence of interhelix loops. It is characterized by a "4 + 1" core, in which four helices form a distorted left-handed supercoil around a central, buried helix. The remaining two helices pack onto the outside of the core. This packing mode is comparable with that proposed for rhodopsin on the basis of two-dimensional electron crystallographic and sequence analysis studies.
authors.affiliation: Laboratory of Molecular Biophysics, University of Oxford, United Kingdom.
authors.forename: M S
authors.initials: MS
authors.lastname: Sansom
authors.forename: H S
authors.initials: HS
authors.lastname: Son
authors.forename: R
authors.initials: R
authors.lastname: Sankararamakrishnan
authors.forename: I D
authors.initials: ID
authors.lastname: Kerr
authors.forename: J
authors.initials: J
authors.lastname: Breed
mesh_terms: D000595:Amino Acid Sequence; D001413:Bacillus thuringiensis / Q000737:chemistry; D000083722:Bacillus thuringiensis Toxins; D001426:Bacterial Proteins / Q000737:chemistry; D001427:Bacterial Toxins; D001436:Bacteriorhodopsins / Q000737:chemistry; D055592:Biophysical Phenomena; D001703:Biophysics; D004731:Endotoxins / Q000737:chemistry; D018257:Helix-Loop-Helix Motifs; D006460:Hemolysin Proteins; D008565:Membrane Proteins / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012243:Rhodopsin / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D000083722:Bacillus thuringiensis Toxins; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004731:Endotoxins; D006460:Hemolysin Proteins; D008565:Membrane Proteins; C030956:insecticidal crystal protein, Bacillus Thuringiensis; D001436:Bacteriorhodopsins; D012243:Rhodopsin