This project will provide insight into the molecular mechanism of ionic conduction in ion channels. The work will be theoretical and will attempt to model the interaction of the permeating ion with different side groups while it travels along the tunnel of the ion channel, driven by an electrochemical gradient. Since the detailed three-dimensional structure of biological ion channels has not yet been determined, the investigator proposes to tackle this problem by using a well studied ion channel with a known 3-D structure (gramicidin A). The proposed studies focus on utilizing a hierarchy of models that will gradually reconstruct permeation up to the ms time range. The modelling attempts will cover: (i) molecular dynamics simulations to generate the paths and energy profiles for the permeating ions, (ii) computation of the Langevin equation using the results of the molecular dynamics simulation, and (iii) to use the theory of renewal processes, to predict measurable parameters such as the probability of occupancy, current/voltage relationships, open channel noise and other measurable single ion channel phenomena. The goal of (i) and (ii) is to evaluate how the structure of the tunnel of a channel changes when it is occupied by ions, and the goal of (iii) is to predict the properties of single ion channels like the rate of transport, selectivity and open channel noise.
