Device engineering approaches to the simulation of charge transport in biological ion channels

Ion channel proteins are naturally occurring nanostructures that regulate the environment of biological cells. The study of ion channels is particularly interesting to device engineers seeking to understand how natural molecular systems realize device-like functions. Every ion channel consists of a chain of amino acids carrying a strong and sharply varying permanent charge, folded in such a way that it creates a nanoscopic aqueous pore spanning the otherwise mostly impermeable membranes of biological cells. Nature has designed many different types of ion channels each with a slightly different physiological role. Most channels exist in two operational states, switching between conducting and non-conducting modes in response to external stimuli, and many can selectively transmit or block a particular ion species. The technique of site-directed mutagenesis offers the capability of altering protein structure and charge one amino acid at a time. Engineering channels with specific conductances and selectivities is therefore a realistic possibility. With the recent availability of high-resolution structural information for several key ion channel proteins and large-scale computational resources, simulations of realistic ion channel systems have also become possible. However, detailed simulation of ion channel behavior over timescales relevant to conduction is very challenging because of the disparate spatial and temporal scales involved. A suitable model hierarchy is desirable to address different simulation needs. In this paper we discuss the various approaches to simulating ion flow in channel systems that are currently being pursued by the biophysics and engineering communities, and present some recent representative simulation results obtained via some of these approaches.