Biophys J, February 2002, p. 628-645, Vol. 82, No. 2

Conducting-State Properties of the KcsA Potassium Channel from Molecular and Brownian Dynamics Simulations

Shin-Ho Chung,^* Toby W. Allen,^* and Serdar Kuyucak

 ^*Department of Physics, Faculty of Sciences, and  Department of Theoretical Physics, Research School of Physical Sciences, Australian National University, Canberra, ACT 0200, Australia

The mechanisms underlying transport of ions across the potassium channel are examined using electrostatic calculations and three-dimensional Brownian dynamics simulations. We first build open-state configurations of the channel with molecular dynamics simulations, by pulling the transmembrane helices outward until the channel attains the desired interior radius. To gain insights into ion permeation, we construct potential energy profiles experienced by an ion traversing the channel in the presence of other resident ions. These profiles reveal that in the absence of an applied field the channel accommodates three potassium ions in a stable equilibrium, two in the selectivity filter and one in the central cavity. In the presence of a driving potential, this three-ion state becomes unstable, and ion permeation across the channel is observed. These qualitative explanations are confirmed by the results of three-dimensional Brownian dynamics simulations. We find that the channel conducts when the ionizable residues near the extracellular entrance are fully charged and those near the intracellular side are partially charged. The conductance increases steeply as the radius of the intracellular mouth of the channel is increased from 2 Å to 5 Å. Our simulation results reproduce several experimental observations, including the current-voltage curves, conductance-concentration relationships, and outward rectification of currents.

Biophys J, February 2002, p. 628-645, Vol. 82, No. 2
© 2002 by the Biophysical Society   0006-3495/02/02/628/18  $2.00

This article has been cited by other articles:

				T. Vora, D. Bisset, and S.-H. Chung Conduction of Na+ and K+ through the NaK Channel: Molecular and Brownian Dynamics Studies Biophys. J., August 15, 2008; 95(4): 1600 - 1611. [Abstract] [Full Text] [PDF]

				M. Hoyles, V. Krishnamurthy, M. Siksik, and S.-H. Chung Brownian Dynamics Theory for Predicting Internal and External Blockages of Tetraethylammonium in the KcsA Potassium Channel Biophys. J., January 15, 2008; 94(2): 366 - 378. [Abstract] [Full Text] [PDF]

				S.-H. Chung and B. Corry Conduction Properties of KcsA Measured Using Brownian Dynamics with Flexible Carbonyl Groups in the Selectivity Filter Biophys. J., July 1, 2007; 93(1): 44 - 53. [Abstract] [Full Text] [PDF]

				T. W. Allen, O. S. Andersen, and B. Roux Ion Permeation through a Narrow Channel: Using Gramicidin to Ascertain All-Atom Molecular Dynamics Potential of Mean Force Methodology and Biomolecular Force Fields Biophys. J., May 15, 2006; 90(10): 3447 - 3468. [Abstract] [Full Text] [PDF]

				B. Corry An Energy-Efficient Gating Mechanism in the Acetylcholine Receptor Channel Suggested by Molecular and Brownian Dynamics Biophys. J., February 1, 2006; 90(3): 799 - 810. [Abstract] [Full Text] [PDF]

				M. O'Mara, B. Cromer, M. Parker, and S.-H. Chung Homology Model of the GABAA Receptor Examined Using Brownian Dynamics Biophys. J., May 1, 2005; 88(5): 3286 - 3299. [Abstract] [Full Text] [PDF]

				V. L. Dorman and P. C. Jordan Ionic Permeation Free Energy in Gramicidin: A Semimicroscopic Perspective Biophys. J., June 1, 2004; 86(6): 3529 - 3541. [Abstract] [Full Text] [PDF]

				B. Corry, M. O'Mara, and S.-H. Chung Conduction Mechanisms of Chloride Ions in ClC-Type Channels Biophys. J., February 1, 2004; 86(2): 846 - 860. [Abstract] [Full Text] [PDF]

				B. Corry, S. Kuyucak, and S.-H. Chung Dielectric Self-Energy in Poisson-Boltzmann and Poisson-Nernst-Planck Models of Ion Channels Biophys. J., June 1, 2003; 84(6): 3594 - 3606. [Abstract] [Full Text] [PDF]

				M. B. Jackson Subtle Shades of Permeability Biophys. J., May 1, 2003; 84(5): 2793 - 2794. [Full Text] [PDF]

				S. Garofoli and P. C. Jordan Modeling Permeation Energetics in the KcsA Potassium Channel Biophys. J., May 1, 2003; 84(5): 2814 - 2830. [Abstract] [Full Text] [PDF]

				T. Bastug and S. Kuyucak Role of the Dielectric Constants of Membrane Proteins and Channel Water in Ion Permeation Biophys. J., May 1, 2003; 84(5): 2871 - 2882. [Abstract] [Full Text] [PDF]

				S. Edwards, B. Corry, S. Kuyucak, and S.-H. Chung Continuum Electrostatics Fails to Describe Ion Permeation in the Gramicidin Channel Biophys. J., September 1, 2002; 83(3): 1348 - 1360. [Abstract] [Full Text] [PDF]

				I. H. Shrivastava, D. P. Tieleman, P. C. Biggin, and M. S. P. Sansom K+ versus Na+ Ions in a K Channel Selectivity Filter: A Simulation Study Biophys. J., August 1, 2002; 83(2): 633 - 645. [Abstract] [Full Text] [PDF]

				S.-H. Chung, T. W. Allen, and S. Kuyucak Modeling Diverse Range of Potassium Channels with Brownian Dynamics Biophys. J., July 1, 2002; 83(1): 263 - 277. [Abstract] [Full Text] [PDF]