**1. Introduction**

Intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) fail to form a stable tridimensional structure, challenging the century-old paradigm that a biological function is a specific property of a unique structure. In spite of the lack of an ordered structure, these proteins exhibit vital biological activities and can be found in all organisms, especially in eukaryotes [1,2]. IDPs and IDRs differentiate from structured proteins and domains, and they are characterized by notable conformational flexibility and structural plasticity. One of the differences of IDPs/IDRs and structured proteins include the amino acid composition since IDPs/IDRs are rich in disorder-promoting residues, such as Arg, Pro, Gln, Gly, Glu, Ser, Ala, and Lys. Also, IDPs/IDRs have low sequence complexity, high net charge, low mean hydropathy and are highly dynamic [2,3].

Many IDPs gain secondary structure when binding onto surfaces, for example, to a cell membrane [2]. Since IDPs/IDRs cannot fold spontaneously and some of them require partners to acquire a more ordered structure, these proteins do not have a code that defines the capacity of foldable proteins to fold spontaneously into a biologically active structure [4]. A typical IDP/IDR has a multitude of elements for potentially foldable, partially foldable, differently foldable, or unfoldable protein segments [5,6]. Their folding can be acquired after the interaction with proteins, nucleic acids, membranes, or small molecules. These conformation modifications can be driven also by changes in the IDPs environment as well as post-translational modifications. These IDPs can remain substantially disordered or become tightly folded after interaction [7–9].

IDPs are difficult proteins to study, due to their dynamic conformational landscapes changing between different structures on a variety of time scales [10,11]. Biophysical studies are crucial to clarify the relationship of the IDPs biological functions and their structures. Recent advances in heteronuclear multidimensional nuclear magnetic resonance (NMR) have allowed the complete assignment of resonances for several IDPs. NMR can also provide data about mobility of the unstructured regions [4,11]. In this way, NMR is possibly the most powerful technique for structural studies of these disordered proteins [12]. Furthermore, computational studies assumed an increasingly importance in interpreting these challenging experimental data [11].
