A Computational Perspective on Drug Discovery and Signal Transduction Mechanism of Dopamine and Serotonin Receptors in the Treatment of Schizophrenia

As the largest family of integral membrane proteins, G-protein-coupled receptors (GPCRs) comprise the largest class of therapeutic targets that aimed approximately 40% of modern medicinal drugs. Understanding the agonist/antagonist mechanism, as well as the signal transduction of the GPCRs, is pivotal in drug discovery and new therapeutic strategy development. In the past few years, determination of high-resolution crystal structures of GPCRs from different subfamilies laid a solid foundation for both experimental and computational studies on GPCR-related diseases. Dopamine and serotonin receptors that belong to class A GPCRs play key roles in psychotic disorders, such as schizophrenia. As a robust approach, computer-aided drug design (CADD) has been demonstrated to be a powerful tool to discover novel drugs against these disorders and to help understand the activation mechanism of related receptors. Herein, we reviewed the recent progresses on CADD-based drug discovery, agonist/antagonist mechanism, and agonist-induced signaling mechanism in dopamine and serotonin receptors.