Molecular Dynamics Simulation Approaches to K Channels

Abstract

Ion channels are proteins that form pores of nanoscopic dimensions in cell membranes. As a consequence of advance in protein crystallography we now know the three-dimensional structures of a number of ion channels. However, X-ray diffraction techniques yield an essentially static (time- and space-averaged) structure of an ion channel, in an environment often somewhat distantly related to that which the protein experiences when in a cell membrane. Thus, additional techniques are required to fully understand the relationship between channel structure and function. Potassium (K) channels (Yellen, 2002) provide an opportunity to explore the relationship between membrane protein structure, dynamics, and function. Furthermore, K channels are of considerable physiological and biomedical interest. They regulate K + ion flux across cell membranes. K channel regulation is accomplished by a conformational change that allows the protein to switch between two alternative (closed vs. open) conformations, a process known as gating. Gating is an inherently dynamic process that cannot be fully characterized by static structures alone. The elucidation of the structures of several K + channels (Mackinnon, 2003;