On the importance of computational biology and bioinformatics to the origins and rapid progression of the intrinsically disordered proteins field

The concept that an unfolded protein could have biological function was proposed by Linus Pauling in 1940. The first experimental evidence for the existence of unfolded proteins, which are now often called intrinsically disordered proteins and regions (IDPs and IDRs), was published in the 1950s. From the 1950s to the 1990s, many additional articles describing IDPs or IDRs were published, and even several Nobel Prizes have been awarded for research on these proteins. The first computational biology/bioinformatics papers on these proteins were reported between 1998 and 2002, and these computational efforts rapidly increased shortly thereafter. In the late 1980s and mid-1990s, a few IDPs and IDRs involved with signaling and regulation were structurally characterized by nuclear magnet resonance (NMR), and these studies demonstrated a likely involvement of IDPs or IDRs in the associated biological regulation. Altogether, the computational biology/bioinformatics and NMR investigations were synergistic in stimulating the rapid increase in the research on IDPs and IDRs. Herein, we describe this history and recent developments in the IDP research arena. We also highlight a recent collection of papers on IDPs and IDRs that are driven by computational biology and bioinformatics efforts.