Normal mode analysis reveals the channel gating motion within a ligand gated ion channel model

Ligand gated ion channels (LGIC) have long been implicated in the mechanisms of general anesthesia. Previous mutational analyses as well as molecular modeling have demonstrated that the site of anesthetic action lies within the transmembrane component of these receptors. Normal mode analyses were performed on our previous model, a LGIC receptor complex. These calculations clearly demonstrated the iris-like wringing motion of the ligand-binding domain relative to the transmembrane domain within the first nontrivial harmonic vibration. This motion was associated with a possible mechanism for native ion channel gating, and the coupling of ligand binding information into ion channel opening. This motion may provide a dynamic paradigm by which entire classes of agonists and antagonists (most notably general anesthetics) exert their effect.