Shaker pore structure as predicted by annealed atomic simulation using symmetry and novel geometric restraints

Biophysical Journal
P K YangM J Hwang

Abstract

Recent studies making use of channel-blocking peptides as molecular calipers have revealed the architecture of the pore-forming region of Shaker-type potassium channels. Here we show that the low-resolution, experimentally derived geometric information can be incorporated as restraints within the context of an annealed molecular dynamics simulation to predict an atomic structure for the channel pore which, by virtue of restraints, conforms to the experimental evidence. The simulation is reminiscent of the computational method employed by nuclear magnetic resonance (NMR) spectroscopists to resolve solution structures of biological macromolecules, but in lieu of restraints conventionally derived from NMR spectra, novel restraints are developed that include side-chain orientation of amino acid residues and assumed symmetry of protein subunits. The method presented here offers the possibility of expanding cooperation between simulation and experiment in developing structural models, especially for systems such as ion channels whose three-dimensional structures may not be amenable to determination by direct methods at the present time.

References

Jun 1, 1992·Protein Engineering·S BoguszD D Busath
Jan 1, 1989·Critical Reviews in Biochemistry and Molecular Biology·G M Clore, A M Gronenborn
Sep 26, 1995·Proceedings of the National Academy of Sciences of the United States of America·G M LipkindH A Fozzard
Jan 1, 1995·Annual Review of Biochemistry·W A Catterall
Feb 1, 1994·Current Biology : CB·M LiL Y Jan
Jul 1, 1994·Protein Engineering·J C Bradley, W G Richards
Aug 1, 1994·Proteins·A M Gronenborn, G M Clore
Mar 11, 1994·Journal of Molecular Biology·N L HarrisF E Cohen
Jan 1, 1994·Biophysical Journal·G M Lipkind, H A Fozzard
Aug 3, 1993·Biochemistry·E T Harper, G D Rose
Dec 19, 1995·Proceedings of the National Academy of Sciences of the United States of America·S ChoeJ M Sullivan
Feb 1, 1996·Neuron·A Gross, R MacKinnon

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Citations

Jun 19, 1998·Current Opinion in Structural Biology·M S Sansom

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