title: Intrinsically disordered proteins: from sequence and conformational properties toward drug discovery.
abstract: Structural disorder of functional proteins under physiological conditions is widespread within eukaryotic proteomes. The lack of stable tertiary and secondary structure offers a variety of functional advantages to intrinsically disordered proteins (IDPs): their malleability of interaction with different partners, specific but low-affinity binding, and their fine modulation by post-translational modifications. IDPs are therefore central players in key processes such as cell-cycle control and signal-transduction pathways, and impairment of their function is associated with many disease states such as cancer and neurodegenerative disorders. Fascinating progress in the experimental characterization of IDPs has been made in the last decade, especially in NMR spectroscopy and small-angle X-ray scattering as well as in single-molecule techniques. It has been accompanied by the development of powerful computational tools to translate experimental results in explicit ensemble representations of IDPs. With the aid of bioinformatics tools, these advances have paved the way to targeting IDP interactions in rational drug-discovery projects.
authors.affiliation: Department for NMR-Based Structural Biology, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Goettingen, Germany. nare@nmr.mpibpc.mpg.de
authors.forename: Nasrollah
authors.initials: N
authors.lastname: Rezaei-Ghaleh
authors.forename: Martin
authors.initials: M
authors.lastname: Blackledge
authors.forename: Markus
authors.initials: M
authors.lastname: Zweckstetter
mesh_terms: D000595:Amino Acid Sequence; D055808:Drug Discovery; D006801:Humans; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D011506:Proteins