We present a framework for computing the gating properties of ligand-gated
ion channel mutants using the Monod-Wyman-Changeux (MWC) model of allostery. We
derive simple analytic formulas for key functional properties such as the
leakiness, dynamic range, half-maximal effective concentration, and effective
Hill coefficient, and explore the full spectrum of phenotypes that are
accessible through mutations. Specifically, we consider mutations in the
channel pore of nicotinic acetylcholine receptor (nAChR) and the ligand binding
domain of a cyclic nucleotide-gated (CNG) ion channel, demonstrating how each
mutation can be characterized as only affecting a subset of the biophysical
parameters. In addition, we show how the unifying perspective offered by the
MWC model allows us, perhaps surprisingly, to collapse the plethora of
dose-response data from different classes of ion channels into a universal
family of curves
