Brownian dynamics study of flux ratios in sodium channels.

Measurements of unidirectional fluxes in ion channels provide one of the experimental methods for studying the steps involved in ion permeation in biological pores. Conventionally, the number of ions in the pore is inferred by fitting the ratio of inward and outward currents to an exponential function with an adjustable parameter known as the flux ratio exponent. Here we investigate the relationship between the number of ions in the pore and the flux ratio exponent in a model sodium channel under a range of conditions.

Conduction of Na+ and K+ through the NaK channel: molecular and Brownian dynamics studies.

Conduction of ions through the NaK channel, with M0 helix removed, was studied using both Brownian dynamics and molecular dynamics. Brownian dynamics simulations predict that the truncated NaK has approximately a third of the conductance of the related KcsA K+ channel, is outwardly rectifying, and has a Michaelis-Menten current-concentration relationship. Current magnitude increases when the glutamine residue located near the intracellular gate is replaced with a glutamate residue.

Estimating the dielectric constant of the channel protein and pore.

When modelling biological ion channels using Brownian dynamics (BD) or Poisson-Nernst-Planck theory, the force encountered by permeant ions is calculated by solving Poisson's equation. Two free parameters needed to solve this equation are the dielectric constant of water in the pore and the dielectric constant of the protein forming the channel. Although these values can in theory be deduced by various methods, they do not give a reliable answer when applied to channel-like geometries that contain charged particles.

Adaptive Brownian dynamics for shape estimation of sodium ion channels.

Ion channels are protein macromolecules that form biological nanotubes across the membranes of living cells. Given many possible geometrical shapes of an ion channel, we propose a computational scheme of selecting the model that best replicates experimental observations, using adaptive Brownian dynamics simulations together with discrete optimization algorithms. Brownian dynamics simulations emulate the propagation of individual ions through the sodium channel nanotube at a femto time second time scale and Angstrom unit (10(-10) meter) spatial scale.

Brownian dynamics investigation into the conductance state of the MscS channel crystal structure.

We suggest that the crystal structure of the mechanosensitive channel of small conductance is in a minimally conductive state rather than being fully activated. Performing Brownian dynamics simulations on the crystal structure show that no ions pass through it. When simulations are conducted on just the transmembrane domain (excluding the cytoplasmic residues 128 to 280) ions are seen to pass through the channel, but the conductance of approximately 30 pS is well below experimentally measured values.

Electrostatic basis of valence selectivity in cationic channels.

We examine how a variety of cationic channels discriminate between ions of differing charge. We construct models of the KcsA potassium channel, voltage gated sodium channel and L-type calcium channel, and show that they all conduct monovalent cations, but that only the calcium channel conducts divalent cations. In the KcsA and sodium channels divalent ions block the channel and prevent any further conduction.

A model of sodium channels.

We have explored the permeation and blockage of ions in sodium channels, relating the channel structure to function using electrostatic profiles and Brownian dynamics simulations. The model used resembles the KcsA potassium channel with an added external vestibule and a shorter selectivity filter. The electrostatic energy landscape seen by permeating ions is determined by solving Poisson's equation.