Computer simulation studies of charge transfer through biological and artificial membrane channels

Biological membrane channels provide the fast and selective exchange of different substances (water, ions, etc...) between intra- and extracellular compartments. Recent determination of the atomic structures of the most important types of membrane channels makes it possible to attempt to derive macroscopically measurable properties of these channels (e.g., ionic current) from their atomic structures and thus to understand the physical mechanism of their action.; In this dissertation such structure-function relationships are studied by means of computer simulation. The limited power of modem supercomputers makes it impossible to simulate actual time-dependent charge transfer through membrane channels using all-atom simulations. In order to overcome this problem an integrated hierarchical approach is used. It combines all-atom MD or QM(EVB)/MM simulations with semi-microscopic calculations of the electrostatic free energy barrier which then is used in stochastic simulations of charge transfer through the channel.; Main results of the dissertation include: (1) an explanation of the mechanism of proton blockage in aquaporin water channels (AQP); (2) application of this mechanism for the theoretical construction of a water nanofilter based on a carbon nanotube membrane; (3) development of the multilevel model for simulation of current and selectivity of single ion channel based on its X-Ray structure and its application to KcsA potassium channel; (4) development of stochastic QM(EVB)/MM models for simulation of proton transport in solution and their application to the proton transport in the gramicidin channel.; The results of the simulations show that in all cases charge (both ion and proton) transport is controlled mainly by electrostatic effects (the interplay between the change of the charge self-energy and the energy of its interactions with protein polar groups).; These results are of interest for both basic science (understanding of fundamental physical mechanisms of charge transport in channels) and for (bio)nanotechnology (artificial water/ion channels).