Simulations of disordered proteins and systems with conformational heterogeneity

• Published in: Current opinion in structural biology 2017-04, Vol.43, p.95-103
• Main Authors: Levine, Zachary A, Shea, Joan-Emma
• Format: Article
• Language: English
• Subjects: Amyloid - chemistry; Amyloid - metabolism; Humans; Intrinsically Disordered Proteins - chemistry; Intrinsically Disordered Proteins - metabolism; Models, Molecular; Protein Conformation
• ISSN: 0959-440X; 1879-033X
• DOI: 10.1016/j.sbi.2016.11.006

•Intrinsically disordered peptides (IDP) lack discernable tertiary structure and populate transient secondary structural elements.•IDP can play both physiological and pathological roles.•Simulations have played a critical role in determining structural ensembles of intrinsically disordered peptides.•Simulations have shed light into IDP function and self-assembly. Intrinsically disordered proteins (IDPs) and protein regions can facilitate a wide variety of complex physiological processes such as binding, signaling, and formation of membraneless organelles. They can however also play pathological roles by aggregating into cytotoxic oligomers and fibrils. Characterizing the structure and function of disordered proteins is an onerous task, primarily because these proteins adopt transient structures, which are difficult to capture in experiments. Simulations have emerged as a powerful tool for interpreting and augmenting experimental measurements of IDPs. In this review we focus on computer simulations of disordered protein structures, functions, assemblies, and emerging questions that, taken together, give an overview of the field as it exists today.