title: A computational perspective on drug discovery and signal transduction mechanism of dopamine and serotonin receptors in the treatment of schizophrenia.
abstract: 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.
authors.forename: Peng
authors.initials: P
authors.lastname: Lian
authors.forename: Lili
authors.initials: L
authors.lastname: Xu
authors.forename: Chuanrong
authors.initials: C
authors.lastname: Geng
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Qian
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Xuechu
authors.initials: X
authors.lastname: Zhen
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, P.R. China. wfu@fudan.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Fu
mesh_terms: D014150:Antipsychotic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D017076:Computer-Aided Design; D055808:Drug Discovery; D006801:Humans; D011954:Receptors, Dopamine / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism*; D012559:Schizophrenia / Q000188:drug therapy* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D014150:Antipsychotic Agents; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin