title: May disordered protein cause serious drug side effect?
abstract: Insomnia is a self-reported disease where patients lose their ability to initiate and maintain sleep, leading to daytime performance impairment. Several drug targets to ameliorate insomnia symptoms have been discovered; however, these drug targets lead to serious side effects. Thus, we characterize the structural properties of these sleep-related receptors and the clock complex and discuss a possible drug design that will reduce side effects. Computational prediction shows that disordered property is shared. Over 30% of the structure of CLOCK, PER1/2/3, BMAL-1, muscarinic acetylcholine receptor-M1, melatonin receptor and casein kinase I are structurally disordered (the remaining proteins represent <30%). Investigations support the principle that the failures of insomnia drugs might be closely related to the protein architecture.
authors.affiliation: School of Medicine, College of Medicine, China Medical University, Taichung, 40402, Taiwan.
authors.forename: Weng Ieong
authors.initials: WI
authors.lastname: Tou
authors.affiliation: School of Medicine, College of Medicine, China Medical University, Taichung, 40402, Taiwan; Department of Biotechnology, Asia University, Taichung, 41354, Taiwan; China Medical University Beigang Hospital, Yunlin, 65152, Taiwan; Computational and Systems Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: ycc929@mit.edu.
authors.forename: Calvin Yu-Chian
authors.initials: CY
authors.lastname: Chen
mesh_terms: D056925:Circadian Rhythm Signaling Peptides and Proteins / Q000737:chemistry* / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects*; D011487:Protein Conformation; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D056925:Circadian Rhythm Signaling Peptides and Proteins; D006993:Hypnotics and Sedatives