This project investigated the structure and functional modulation of pentameric ligand-gated ion channels (pLGICs)—membrane proteins that convert chemical signals into electrical responses and represent key drug targets in humans. Using an integrated methodological approach that combined small-angle neutron scattering (SANS), cryo-electron microscopy (cryo-EM), electrophysiology, and molecular dynamics simulations, the research explored the bacterial model systems GLIC and DeCLIC to reveal how these proteins function and respond to modulators such as general anaesthetics.
Neutron scattering and simulation data were used together to describe the solution structures and conformational flexibility of the channels, while cryo-EM identified new structural states, including an open conformation of DeCLIC consistent with scattering observations.
By merging experimental and computational perspectives, this work deepened the understanding of allosteric modulation and structural dynamics in ion channels and advanced methodologies for integrating neutron scattering and simulations in the study of complex membrane proteins.