Exploring the activation mechanisms of pentameric ligand gated ion channels (pLGICs) by atomistic simulations and single channel methods

Carla Molteni (primary)
King's College London
Lucia Sivilotti (secondary)
Division of Biosciences, Department of Neuroscience Physiology and Pharmacology
University College London


pLGICs are important neuroreceptors, embedded in neuronal membranes where they mediate fast synaptic communication. They are involved in many neurological disorders and are targets sites for drugs. However, due to their complexity and the limited structural information available, how they function at the molecular level is still far from being fully understood. In this PhD project we will focus on a specific pLGIC, the glycine receptor, with the goal to understand how the binding of glycine activates the receptor and opens its channel. We will achieve this by a unique combination of innovative computational techniques and single channel experiments.


Federico Comitani, Vittorio Limongelli and Carla Molteni, “The Free Energy Landscape of GABA Binding to a Pentameric Ligand-gated Ion Channel and its Disruption by Mutations”, J. Chem. Theory Comput. 12, 3398-3406 (2016). DOI: 10.1021/acs.jctc.6b00303
Alessandro Crnjar, Federico Comitani, Claudio Melis and Carla Molteni, “Mutagenesis Computer Experiments in Ligand-Gated Ion Channels: the Role of Simulation Tools with Different Resolution”, Interface Focus 9, 20180067 (2019). DOI: 10.1098/rsfs.2018.0067
Alessandro Crnjar, Federico Comitani, William Hester and Carla Molteni, “Trans-cis Proline Switches in a Pentameric Ligand-Gated Ion Channel: how They are Affected by and how They Affect the Biomolecular Environment”, J. Phys. Chem. Lett. 10, 3, 694-700 (2019). DOI: 10.1021/acs.jpclett.8b03431
Remigijus Lape, David Colquhoun and Lucia Sivilotti, “On the Nature of Partial Agonism in the Nicotinic Superfamily” Nature 454, 722-727 (2008). DOI: 10.1038/nature07139
Michael Epstein, Ben Calderhead, Mark Girolami and Lucia Sivilotti, “Bayesian Statistical Inference in Ion-Channel Models with Exact Missed Event Correction” Biophysical J., 111,333-48 (2016). DOI: 10.1016/j.bpj.2016.04.053

Animal disease, health and welfare
Area of Biology
Chemical BiologyNeurobiology
Techniques & Approaches
BiochemistryBiophysicsSimulation / Modelling