Our research focuses on the discovery of new small molecules targeting the GDNF signalling for the treatment of schizophrenia. We discovered that strong dopaminergic factor GDNF is increased in schizophrenia (SCZ) patients and that in mice similar increase in GDNF results in SCZ like features. Thus, modulating GDNF signalling may treat GDNFhigh subgroup of SCZ, but suitable drugs are not available. We have already discovered a series of compounds capable to modulate GDNF signalling. Our goals are to improve the understanding of the GDNF signalling by identifying enhanced small molecule modulators through structure-based and ligand-based computational approaches. We will combine molecular docking, similarity-based searches and machine-learning approaches for ligand discovery and hit-to-lead optimization. New Candidates from the simulations will be experimentally tested in our lab. Our current research is funded by Hjärnfonden.