Membrane Protein Simulations: Ion Channels And Bacterial Outer Membrane Proteins

Abstract

The chapter focuses on two classes that have been investigated by a number of research groups—namely, ion channels and bacterial outer membrane proteins—rather than attempt to cover all simulations of membrane proteins. Ion channels play a key role in the electrical activity of cells of the nervous system. However, channels are also found in the membranes of non-excitable cells and a wide range of organisms from viruses to plants. The chapter focuses on simulation studies of a bacterial K channel, KcsA, and of related K channel species. Gram-negative bacterial cells are enclosed by two membranes. The outer membrane is highly asymmetric, whereas its inner leaflet has a similar phospholipid composition to that of the inner membrane: its outer leaflet contains lipo-polysaccharide molecules. A combination of molecular modeling and simulation helps us to extrapolate from the structure of prokaryotic membrane proteins to the structure and dynamics of their human homologues, which may also aid in experimental structure determination. Ultimately, simulation offers the prospect of understanding the effects of mutations on physiological function in a variety of disease states, as well as aiding the discovery and design of drugs to help combat such diseases.