Despite technological advances, industry has failed to produce new pharmaceuticals and novel strategies for drug development are desperately needed. We believe that the focus of early-phase drug discovery needs to be shifted towards new approaches for lead discovery and identification of novel mechanisms for target modulation. We focus our efforts on G protein-coupled receptors (GPCRs), which are involved in numerous physiological processes and the targets of 30% of all drugs. The goal of our research is to improve atomic-level understanding of GPCR-ligand interactions using computer models with the vision to increase knowledge of the function of these proteins and develop new strategies for drug discovery. Using atomistic MD simulations, we gain molecular level understanding of how small molecules interact with GPCRs and thereby modulate their function. By combining protein structure prediction with virtual screening methods, we predict new drug candidates to pharmaceutically relevant GPCRs and test these experimentally. Our research projects are driven by computational chemistry and carried out in close collaboration with experimental groups.