Function of the acetylcholine receptor at the atomic scale

The three fundamental steps underlying ion channel function comprise sensing of the stimulus, transduction of the stimulus into a change in conductance state and selection of particular ions for translocation. Recent work from our laboratory implemented a variety of molecular simulation methods to study all three steps. First we use all-atom molecular dynamics simulation to follow trajectories of single ions along the ion translocation pathway, and so reveal structural and dynamic counterparts of ion selectivity and translocation processes. Second we use an accelerated simulation algorithm to mimic the stimulus, and then examine the resulting structural changes in the ion translocation pathway. Third we used a coarse-grained ion channel simulator to determine whether the altered pore was selectively permeable to cations. The overall findings highlight the power of computational methods to reveal atomic scale aspects of ion channel function, as well as to generate hypotheses amenable to experimental testing. Continued advances in computational speed and analysis methods hold the promise to paint an increasingly vivid picture of the functioning of ion channels at the atomic scale.