7-HELIX BUNDLES - MOLECULAR MODELING VIA RESTRAINED MOLECULAR-DYNAMICS

Simulated annealing via restrained molecular dynamics (SA/MD) has been used to model compact bundles of seven approximately (anti)parallel a lpha-helices. Seven such helix bundles occur, e.g., in bacteriorhodops in, in rhodopsin, and in the channel-forming N-terminal domain of Baci llus thuringiensis delta-endotoxin. Two classes of model are considere d: (a) those consisting of seven Ala(20) peptide chains; and (b) those containing a single polypeptide chain, made up of seven Ala(20) helic es linked by Gly(N) interhelix loops (where N = 5 or 10). Three differ ent 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 ens embles of models generated by SA/MD are analyzed in terms of their geo metry and energetics, and the most stable structures from each ensembl e are examined in greater detail. Structures resembling bacteriorhodop sin and structures resembling delta-endotoxin are both represented amo ng the most stable structures. delta-Endotoxin-like structures arise f rom both circular and bacteriorhodopsin-like C alpha templates. A thir d helix-packing mode occur; 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 ten-handed supercoil around a central, burie d helix. The remaining two helices pack onto the outside of the core. This packing mode is comparable with that proposed for rhodopsin on th e basis of two-dimensional electron crystallographic and sequence anal ysis studies.