Computational Electrophysiology: Close-UPS of Ion Permeation and Migration in Membrane Proteins

Abstract

The function of ion channels underpins electrical signalling across the membrane and shapes the transmembrane potential. Ion channels are involved in a broad range of physiological processes, and their malfunction is linked to a variety of diseases. Investigating their function and interactions has thus become an important interdisciplinary research area, and a broad spectrum of molecular simulation methods are applied to study gating and permeation in channel proteins. I will give an overview over the principles and use of Computational Electrophysiology (CompEl), a method that enables the atomistic simulation of ion channel currents driven by transmembrane electrochemical potentials [1]. The protocol has recently been implemented in the popular molecular dynamics software Gromacs. I will then present recent findings on channel permeation mechanisms [2,3] and ion migration in signalling proteins, which were obtained by applying CompEl in extended atomistic simulations.[1] C. Kutzner et al., Biophys J 101, 809-817 (2011).[2] C. Song et al., Proc Nat Acad Sci 110, 4586-4591 (2013).[3] D.A. Kopfer et al., Science 346, 352-355 (2014).