The nerve cells in the brain communicate with each other by the help of transmitter substances. The neurotransmitter serotonin affects widely different proteins in the central nervous system, and helps control our mood, sex drive, appetite and emotional behavior. A large number of pharmaceuticals, used in the treatment of diseases like anxiety, depression, migraine and obesity, have a complicated mechanism of effect and affects many different proteins in the serotonergic system. In this project, we will make use of brand new crystal structures of related proteins to create molecular models for an array of representative proteins in the serotonergic system. With a combination of techniques from molecular biology, pharmacology and computational modeling, we will describe how selected drugs act on a broad selection of the serotonergic proteins. By comparing very selective drugs med multimodal drugs that affect more than one protein, we obtain a deeper understanding of the parameters governing drug selectivity towards the many proteins in the serotonergic system. This will in the long run be pivotal for rational development of multimodal drugs with a tailored selectivity profile that have the potential to show increased effects and fewer side effects compared to current methods of treatment. The project will be carried out as a joint project between experts in molecular modeling at Aarhus University and in chemical biology at Copenhagen University, in collaboration with leading international partners in industry and academia.