Simultaneous quantification of protein order and disorder.

The discovery of disordered proteins, which constitute about one-third of the human proteome and are crucial for regulation and signaling1–3, has profoundly shaken the long-held paradigm that proteins fold into well-defined native structures whose atomic coordinates can be determined almost univocally. This finding has been followed by a polarization of the terms ‘order’ and ‘disorder’, which, in hindsight, has been largely prompted by a lack of techniques capable of fully characterizing the dynamics of proteins. Protein disorder was initially defined as ‘absence of structure’, for example, from regions of missing coordinates in native structures determined through X-ray crystallography1–3. Such a definition implies that order and disorder are mutually exclusive, while in fact protein structures and dynamics are closely related and central to the functions of these molecules. In this Commentary, we discuss how the development of methods capable of simultaneously determining structure and dynamics of proteins, including, in particular, nuclear magnetic resonance (NMR) spectroscopy, is gradually making it possible to supersede this rather artificial polarization between order and disorder. We anticipate that the introduction of increasingly quantitative descriptions of structure and dynamics will provide compelling insights into the molecular mechanisms underlying protein behavior.