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Although there is a large body of site-directed mutagenesis data that identify the pore-lining sequence of the voltage-gated potassium channel, the structure of this region remains unknown. We have interpreted the available biochemical data as a set of topological and orientational restraints and employed these restraints to produce molecular models of the potassium channel pore region, H5. The H5 sequence has been modeled either as a tetramer of membrane-spanning beta-hairpins, thus producing an eight-stranded beta-barrel, or as a tetramer of incompletely membrane-spanning alpha-helical hairpins, thus producing an eight-staved alpha-helix bundle. In total, restraints-directed modeling has produced 40 different configurations of the beta-barrel model, each configuration comprising an ensemble of 20 structures, and 24 different configurations of the alpha-helix bundle model, each comprising an ensemble of 24 structures. Thus, over 1300 model structures for H5 have been generated. Configurations have been ranked on the basis of their predicted pore properties and on the extent of their agreement with the biochemical data. This ranking is employed to identify particular configurations of H5 that may be explored further as models of the pore-lining region of the voltage-gated potassium channel pore.

Original publication

DOI

10.1016/S0006-3495(97)78095-0

Type

Journal article

Journal

Biophys J

Publication Date

08/1997

Volume

73

Pages

581 - 602

Keywords

Amino Acid Sequence, Computer Simulation, Electric Conductivity, Models, Structural, Molecular Sequence Data, Mutagenesis, Site-Directed, Potassium Channels, Protein Structure, Secondary, Recombinant Proteins, Reproducibility of Results, Shaker Superfamily of Potassium Channels, Software