Computer simulation of ion conductance in membrane channels

Hoyles, Matthew; Kuyucak, Serdar; Chung, Shin-Ho

doi:10.1103/physreve.58.3654

Cited by 64 publications

(84 citation statements)

References 16 publications

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“…The electrostatic potential energy profile for various ion configurations in the channel is calculated from the numerical solutions of Poisson's equation by using the boundary element method (29). Energies of multiple ion systems are calculated with a steepest descent algorithm (3).…”

Section: Methodsmentioning

confidence: 99%

“…The Langevin equation is solved with the algorithm of van Gunsteren and Berendsen (30), by using the techniques described elsewhere (3,31,32). Electrostatic forces are determined by solving Poisson's equation with the boundary sector method (33), employing lookup table techniques (29,35). To simulate the effects of short-range forces, we employ a multiple time-step algorithm, where a short time-step of 2 fs is used in the narrow selectivity filter and a long time-step of 100 fs is used in the outer and inner vestibules and reservoirs.…”

Section: Methodsmentioning

confidence: 99%

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A model of the glycine receptor deduced from Brownian dynamics studies

O’Mara

Barry

Chung

2003

Proc. Natl. Acad. Sci. U.S.A.

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We have developed a three-dimensional model of the ␣1 homomeric glycine receptor by using Brownian dynamics simulations to account for its observed physiological properties. The model channel contains a large external vestibule and a shallow internal vestibule, connected by a narrow, cylindrical selectivity filter. Three rings of charged residues from the pore-lining M2 domain are modeled as point charges in the protein. Our simulations reproduce many of the key features of the channel, such as the currentvoltage profiles, permeability ratios, and ion selectivity. When we replace the ring of alanine residues lining the selectivity filter with glutamates, the mutant model channel becomes permeable to cations, as observed experimentally. In this mutation, anions act as chaperones for sodium ions in the extracellular vestibule, and together they penetrate deep inside the channel against a steep energy barrier encountered by unaccompanied ions. Two subsequent amino acid mutations increase the cation permeability, enabling monovalent cations to permeate through the channel unaided and divalent cations to permeate when chaperoned by anions. These results illustrate the key structural features and underlying mechanism for charge selectivity in the glycine receptor.ligand-gated ion channels ͉ conductance ͉ permeation I n recent years, enormous strides have been made in our understanding of the structure-function relationships in biological ion channels. The determination of the structures of several different classes of ion channels and concurrent advances in computational biophysics have prompted numerous theoretical investigations that have shed considerable light on mechanisms of permeation and selectivity. Among these are the thermodynamics of cation permeation through the selectivity filter (1), macroscopic studies of energy profiles in the pore (2-4), semimicroscopic simulations to elucidate the mechanisms of ion permeation and selectivity (4-7), and molecular dynamics calculations focusing on permeation (8)(9)(10)(11)(12)(13)(14). In addition, threedimensional Brownian dynamics simulations have been fruitfully used to construct a model of the L-type calcium channel (15, 16). These theoretical studies are reviewed in several recent articles (17)(18)(19)(20).One class of proteins that has been neglected in theoretical investigations is that of anion-selective channels. Important members of the ligand-gated anion channel family include the ␥-aminobutyric acid (GABA) and glycine receptors, which mediate hyperpolarizing synaptic potentials in response to neurotransmitters. Although the crystal structures of the glycine and GABA receptors are not yet determined, the experimental findings and the high similarity of these channels to the nicotinic acetylcholine receptor allow us to make a reasonable conjecture on their approximate shape and the locations of dipoles and charged residues lining the channel wall. Like the acetylcholine receptor (21), which belongs to the same superfamily, the glycine receptor (GlyR) is like...

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

A model of the glycine receptor deduced from Brownian dynamics studies

O’Mara

Barry

Chung

2003

Proc. Natl. Acad. Sci. U.S.A.

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“…To reduce these requirements, Chung and co-workers assumed an azimuthal symmetry of the dielectric boundary and store the reaction field Green's function in a fivedimensional table. 6,7,10,17 These difficulties are circumvented by expressing the ion charge distribution in the simulation region using a normalized basis set ͕b m (r)͖ with N basis functions,…”

Section: ͑13͒mentioning

confidence: 99%

“…To avoid this problem, Chung and co-workers have used an interpolation method and a large look-up table to store a discretized representation of the Green's function of the system. 6,7,10,17 The reaction field energy of a given ion configuration can be reconstructed from the stored information. A similar method was used by Coalson and co-workers.…”

Section: Introductionmentioning

confidence: 99%

Brownian dynamics simulations of ions channels: A general treatment of electrostatic reaction fields for molecular pores of arbitrary geometry

Im¹,

Roux²

2001

The Journal of Chemical Physics

105

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A general method has been developed to include the electrostatic reaction field in Brownian dynamics ͑BD͒ simulations of ions diffusing through complex molecular channels of arbitrary geometry. Assuming that the solvent is represented as a featureless continuum dielectric medium, a multipolar basis-set expansion is developed to express the reaction field Green's function. A reaction field matrix, which provides the coupling between generalized multipoles, is calculated only once and stored before the BD simulations. The electrostatic energy and forces are calculated at each time step by updating the generalized multipole moments. The method is closely related to the generalized solvent boundary potential ͓Im et al., J. Chem. Phys. 114, 2924 ͑2001͔͒ which was recently developed to include the influence of distant atoms on a small region part of a large macromolecular system in molecular dynamics simulations. It is shown that the basis-set expansion is accurate and computationally inexpensive for three simple models such as a spherical ionic system, an impermeable membrane system, and a cylindrical pore system as well as a realistic system such as OmpF porin with all atomic details. The influence of the static field and the reaction field on the ion distribution and conductance in the OmpF channel is studied and discussed.

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“…The value is reduced to 0.1 of the bulk value in the narrow selectivity filter and 0.5 of the bulk value elsewhere in the channel, as determined by molecular dynamics calculations [16]. For further details of stochastic dynamics simulations, see Hoyles et al [17].…”

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confidence: 99%