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Proposing Institution

Institut für Medizinische Physik und Biophysik, Charité
Project Manager

Prof. Dr. Peter Hildebrand
Chariteplatz 1
10117 Berlin
G-protein coupled receptors (GPCRs) constitute the largest protein family in the human genome. The ProteInformatics group located at the Institute of Medical Physics and Biophysics of the Charité University Medicine Berlin, has received international recognition in addressing the functionality and pharmacology of GPCRs using molecular dynamics (MD) simulations. Previous participations in projects on HLRN (Projects: bec00085 2012-2016) and SuperMUC (Dr. Saleh: pr94to, pr74su), have demonstrated the great potential of MD simulations and enhanced sampling methods to describe structure function relationships of GPCRs based on their conformational dynamics. This aspect cannot be addressed by classical structural biology methods such as X-ray crystallography. The results of our previous projects shed a light on the molecular basis and involvement of the GPCRs conformational flexibility in ligand binding and specific signal transduction. Combining the schemes previously prototyped, we now aim to elucidate (i) the structural intermediates of the Rhodopsin activation cycle and (ii) the structural basis of functional selectivity tuned by newly developed dual-steric ligands for the Muscarinic M2 receptor (M2R). Our models will assist the experimental efforts in the laboratories of Prof. Brian Kobilka (Stanford University – Noble Laureate in Chemistry 2012) and Prof. Jesper Mosolff Mathiesen (University of Copenhagen), whose complementary methods will serve to validate our in silico predictions

Impressum, Conny Wendler