# Monod-Wyman-Changeux Analysis of Ligand-Gated Ion Channel Mutants

## TL;DR

This paper introduces an analytical framework based on the Monod-Wyman-Changeux model to analyze how mutations affect ligand-gated ion channels, unifying diverse dose-response data into a universal perspective.

## Contribution

It provides simple formulas for key functional properties and demonstrates how mutations influence specific biophysical parameters across different ion channels.

## Key findings

- Analytic formulas for leakiness, dynamic range, EC50, and Hill coefficient.
- Mutations can be characterized by their effects on specific parameters.
- Dose-response data from various channels collapse into a universal family of curves.

## Abstract

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.