| Standard Poisson-Nernst-Planck (PNP) theory is modified by adding contributions due the Dielectric Self Energy and dynamic relaxation of a protein channel in response to ion permeation. This approach is utilized to predict ionic currents through the Gramicidin A (GA) channel, in which the applicability of conventional continuum theories is questionable. The Potential of Mean Force for K+ and Cl- ions in GA are obtained by combining an equilibrium molecular dynamics (MD) simulation that samples dynamic protein configurations with a continuum electrostatic calculation of the free energy. The results of our study show that the channel response to the permeating ion produces significant electrostatic stabilization of K+ inside the channel.;The local diffusion constant of K+ inside the GA channel has been calculated using four different computational methods based on MD simulations: Mean Square Displacement (MSD), Velocity Autocorrelation Function (FACF), Second Fluctuation Dissipation Theorem (SFDT) and analysis of the Generalized Langevin Equation for a Harmonic Oscillator (GLE-HO). All methods were tested and compared in bulk water and all predicted the correct diffusion constant. Inside GA, MSD and VACF methods were found to be unreliable because they are biased by the systematic force exerted by the channel system. SFDT and GLE-HO methods properly unbias the influence of systematic force and predicted a similar diffusion constant of K+ inside GA, namely, ca. 10 times smaller than in the bulk.;A simplified three-dimensional model of ClC chloride channel was constructed to couple the ion permeation to the motion of a glutamate side chain which acts as the putative fast gate. Dynamic Monte Carlo (DMC) simulations were carried out using this model channel to investigate the dependence of the gate closing rate on internal and external chloride concentration as well as the gate charge. Our simulation results were in qualitative agreement with experimental observations and consistent with the "foot-in-the-door" mechanism.;Osmotic and diffusion permeabilities of H2O and D2O in Aquaporin 1 (AQP1) were calculated using MD simulations and, subsequently, osmotic permeabilities were measured experimentally. The combined computational and experimental results suggest that D2O permeability through AQP1 is similar to that of water. |
