Looking at the finer details of ligand:receptor interactions

Docking calculations to predict ligands for G protein-coupled receptors (GPCRs) have become a widely used technique in recent years. Yet, for each new receptor system and receptor conformation the question remains how to best prepare a system to enrich ligands over non-binders. Moreover, particularly in settings where (known) ligands should be docked individually and with high precision in order to enable further development, small details can determine success or failure. I will present to cases where we have investigated the roles of conformation, presence of water molecules and protonation states of amino acids and will highlight what we think are commonly applicable conclusions.