Viral ion channels: molecular modeling and simulation

In a number of membrane-bound viruses, ion channels are formed by integral membrane proteins. These channel proteins include M2 from influenza A, NE f rom influenza B, and, possibly, Vpu from HIV-1, M2 is important in facilita ting uncoating of the influenza A viral genome and is the target of amantad inet an anti-influenza drug, The biological roles of NE and Vpu are less ce rtain. In all cases, the protein contains a single transmembrane alpha-heli x close to its N-terminus. Channels can be formed by homo-oligomerization o f these proteins, yielding bundles of transmembrane helices that span the m embrane and surround a central ion-permeable pore. Molecular modeling may b e used to integrate and interpret available experimental data concerning th e structure of such transmembrane pores. This has proved successful for the M2 channel domain, where two independently derived models are in agreement with one another, and with solid-state nuclear magnetic resonance (NMR) da ta. Simulations based on channel models may yield insights into possible io n conduction and selectivity mechanisms, BioEssays 20:992-1000, 1998. (C) 1 998 John Wiley & Sons, Inc.