title: Targeting intrinsically disordered proteins in rational drug discovery.
abstract: BACKGROUND
  Intrinsically disordered proteins (IDPs) and intrinsically disordered protein regions (IDPRs) have gained wide recognition over the past decade due to their versatile roles in cell physiology and pathology. A large repertoire of IDPs/IDPRs has been implicated in numerous diseases, making them potential targets for therapeutic intervention. Recent advances in experimental methods and computational approaches have enabled detection and characterization of these highly dynamic proteins at atomistic detail, thus facilitating disorder/dynamic-based drug discovery.
  
  
  METHODS
  This article presents an overview of the functional relevance and pathological implications of IDPs/IDPRs in cells. The authors outline the currently available experimental methods employed for structural characterization of these proteins. They also exemplify the practical limitations encountered during such characterization and ways to overcome them. Taken together, the article discusses the plausibility of exploiting protein disorder for drug targeting.
  
  
  CONCLUSIONS
  Disorder-based drug targeting is gearing up in the realm of novel drug discovery approaches. Tools for probing the molecular features of IDPs and IDPRs are rapidly improving and start to provide accurate descriptions of the complex ensembles populated by IDPs/IDPRs. They thus pave the way for the development of drug molecules, which specifically target disease-associated disorder.
authors.affiliation: a German Center for Neurodegenerative Diseases (DZNE) , 37077 Göttingen , Germany.
authors.forename: Susmitha
authors.initials: S
authors.lastname: Ambadipudi
authors.affiliation: a German Center for Neurodegenerative Diseases (DZNE) , 37077 Göttingen , Germany.|b Department for NMR-based Structural Biology , Max Planck Institute for Biophysical Chemistry , 37077 Göttingen , Germany.|c DFG Research Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB) , University Medical Center Göttingen , 37073 Göttingen , Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Zweckstetter
mesh_terms: D000818:Animals; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D064267:Intrinsically Disordered Proteins / Q000378:metabolism*; D008958:Models, Molecular; D058990:Molecular Targeted Therapy; D011487:Protein Conformation
chemical_list: D064267:Intrinsically Disordered Proteins
keywords: NMR spectroscopy; drug discovery; intrinsically disordered protein; neurodegeneration