A Computational Perspective on Drug Discovery and Signal Transduction Mechanism of Dopamine and Serotonin Receptors in the Treatment of Schizophrenia
Peng Lian, Lili Xu, Chuanrong Geng, Yuanyuan Qian, Wei Li, Xuechu Zhen, Wei Fu · Current Pharmaceutical Biotechnology · 2014
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.