13 September 2022
Dr. David Thal
Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville)
Cryo-EM has revolutionised the determination of protein structures and holds great promise for structure-based drug discovery. Recent structural studies from their group, utilising cryo-EM to determine the structures of therapeutically relevant protein targets in complex with novel chemical ligands, will be presented. This will include examples from different types of proteins, including G protein-coupled receptors (GPCRs), ion channels, and soluble enzymes. Specific examples will include cases where the cryo-EM structures revealed ligands in expected binding sites, ligands in unexpected binding sites, unexpected ligands in expected binding sites, no ligand at any site, and examples in between. Validating these ligand binding sites and current limitations, will also be discussed.