Pentameric ligand-gated ion channels: insights from computation

Pentameric ligand-gated ion channels (pLGICs) conduct upon the binding of an agonist and are fundamental to neurotransmission. New insights into the complex mechanisms underlying pLGIC gating, ion selectivity and modulation have recently been gained via a series of crystal structures in prokaryotes and Caenorhabditis elegans, as well as computational studies relying on these structures. Here, we review contributions from a variety of computational approaches, including normal-mode analysis, automated docking and fully atomistic molecular dynamics simulation. Examples from our own research, particularly concerning interactions with general anaesthetics and lipids, are used to illustrate predictive results complementary to crystallographic studies.