Ion channel dynamics and function

The biological viewpoint of the potassium channel ($K^{+}$ channel) has been carefully studied. $K^{+}$ channels are very important in allowing the flow of potassium ions in human cells, but excluding other ions such as sodium ions. These channels are crucial in maintaining normal cardiac rhythm because they are voltage sensitive and control the re-polarization of our nerves after the generation of action potential. However, much of the protein forming the $K^{+}$ channel has not been treated explicitly in computer simulations. Simulations have only been done on the permeation aspect of the channels and its selectivity feature [2]. The selectivity filter is only several amino acids compared to the whole sequence of 160 amino acids per each subunit of the channel. The limitations are due to the lack of the information in the X-ray structure published in 1998 [27] and the costs of computing time and resources. Both the accuracy and the time scale of the simulations may have to be sacrificed if the simulation is done at the atomic level. Present atomic level molecular dynamics can only simulate at the time scale of nanosecond, while the gating mechanism of the channel is at the time scale of millisecond. We will use our multiscale semi-implicit method coupled with constrained dynamics to study permeation and gating mechanisms of this channel. We will also compare the treatment of high frequencies to Elber's reaction path method described above. See Sections 2.4.1 and 3.5.1.