Ion channels are membrane proteins that establish a resting membrane potential and navigate electrical signals by gating the flow of ions across the cell membrane. By using molecular dynamics (MD) based computational simulations we aim to understand how the ions pass through the channels and how channels respond to chemical and electrical forces at the atomic level.
For example, we simulated the ion permeation process of K2P channels, which in combination with results from electrophysiology revealed a novel voltage-gating mechanism by which ion channels can sense voltage without containing a voltage sensor domain (Schewe et al., Cell, 2016).
Furthermore, we studied NaK which belongs to the class of non-selective monovalent cation channels that conduct both K+ and Na+ ions with equal efficiency. By a combination of solid-state NMR spectroscopy and MD simulations, we showed that the selectivity filter of NaK in native-like lipid membranes adopts two distinct conformations that are stabilized by either Na+ or K+ ions. We resolved the atomic structural differences of these conformations and proposed that the structural plasticity of the selectivity filter in NaK is the key molecular determinant for its ion non-selectivity (Shi et al., Nat. Commun., 2018).
Currently, we are particularly interested in the permeation properties of AMPA receptors. Permeation of ions through AMPA receptors dissipates as much as 30% of the brain energy demand and AMPA receptor permeability is implicated in synaptic plasticity, learning, and disease. This project is performed in close collaboration with the experimental electrophysiology and biophysics group of Prof. Dr. Andrew Plested.