TY  - JOUR
AU  - Ambadipudi, Susmitha
AU  - Zweckstetter, Markus
TI  - Targeting intrinsically disordered proteins in rational drug discovery.
JO  - Expert opinion on drug discovery
VL  - 11
IS  - 1
SN  - 1746-0441
CY  - Abingdon
PB  - Taylor & Francis Group
M1  - DZNE-2020-04636
SP  - 65-77
PY  - 2016
AB  - 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.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.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.
KW  - Animals
KW  - Drug Design
KW  - Drug Discovery: methods
KW  - Humans
KW  - Intrinsically Disordered Proteins: metabolism
KW  - Models, Molecular
KW  - Molecular Targeted Therapy
KW  - Protein Conformation
KW  - Intrinsically Disordered Proteins (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:26549326
DO  - DOI:10.1517/17460441.2016.1107041
UR  - https://pub.dzne.de/record/138314
ER  -