Computerstudien zur Physik von Ionenkanälen

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Ion permeation in channels and porins is involved in key biological processes, such as nerve impulse, cardiac and smooth muscle contraction. To advance in our understanding it is crucial to link structural and molecular biologists to groups involved in molecular simulation. Here we plan to study ion permeation through the porin NanC from E. coli by computational methods, in collaboration with molecular biologists performing experiments in Chicago, US. We will calculate the free energy associated with Na+ and K+ ion permeation based on the available structural information. We will use not only force-field based molecular dynamics simulations but also tools of quantum mechanics available in my group. The latter calculations will address key issues regarding the force field accuracy of the ions. This work will be complemented by the simplified models developed by Bob Eisenberg and coworkers aimed at calculating ion currents (e.g. Density Functional of Fluid-Poisson-Nernst-Planck theory). Comparison between free energy permeation profiles will lead to understanding of each method, and of the channel function itself. Then, using theory and experiments, we will attempt at engineering the protein to a Na+ selective channel.