Start of funding 01.01.2024

Application of alchemical free energy methods for the development of new G protein-biased µ opioid receptor agonists

Prof. Dr. Peter Gmeiner
Friedrich-Alexander-University of Erlangen-Nuremberg
Department Chemie und Pharmazie

Prof. Dr. Michael K. Gilson
University of California, San Diego
Skaggs School of Pharmacy and Pharmaceutical Sciences



The G-protein-coupled µ-opioid receptor is responsible for both the analgesic effect of opioids such as morphine and fentanyl and their side effects, including addictive potential. While the analgesic effect is mediated via the G-protein signaling pathway, ß-arrestin transmits the side effects. The Gmeiner laboratory, which specializes in the development of novel GPCR ligands, succeeded in developing the G-protein-selective compound PZM21. The Gilson lab develops and uses computational chemistry methods to determine the binding affinity of new chemical compounds, also taking into account water displacement. As part of the collaboration, methods from the Gilson Lab will be used to further optimize PZM21 and investigate the signaling behavior of the µ-opioid receptor. The final goal will be the development of a new pain medication.