The term'undruggable'was coined to describe proteins that could not be targeted
pharmacologically. However, progress is being made to'drug'many of these targets, and …

Highlights•The principles of protein structural ensemble determination are described.•The
use of experimental data averaged over multiple states is analysed.•Approaches for …

A wide range of proteins have been reported to condensate into a dense liquid phase,
forming a reversible droplet state. Failure in the control of the droplet state can lead to the …

Alzheimer's disease is a neurodegenerative disorder associated with the aberrant
aggregation of the amyloid-β peptide. Although increasing evidence implicates cholesterol …

Abstract Structure-based drug design has often been restricted by the rather static picture of
protein–ligand complexes presented by crystal structures, despite the widely accepted …

Broad conformational ensembles make intrinsically disordered proteins or regions
entropically intriguing. Although methodologically challenging and understudied, emerging …

Solid-like protein deposits found in aged and diseased human brains have revealed a
relationship between insoluble protein accumulations and the resulting deficits in neurologic …

Intrinsically disordered proteins (IDPs) and multidomain proteins with flexible linkers show a
high level of structural heterogeneity and are best described by ensembles consisting of …

Disordered proteins are challenging therapeutic targets, and no drug is currently in clinical
use that modifies the properties of their monomeric states. Here, we identify a small …

Intrinsically disordered proteins (IDPs) are implicated in many human diseases. They have
generally not been amenable to conventional structure-based drug design, however …