Back to the Future: Nuclear Magnetic Resonance and Bioinformatics Studies on Intrinsically Disordered Proteins

From the 1970s to the present, regions of missing electron density in protein structures determined by X-ray diffraction and the characterization of the functions of these regions have suggested that not all protein regions depend on prior 3D structure to carry out function. Motivated by these observations, in early 1996 we began to use bioinformatics approaches to study these intrinsically disordered proteins (IDPs) and IDP regions. At just about the same time, several laboratory groups began to study a collection of IDPs and IDP regions using nuclear magnetic resonance. The temporal overlap of the bioinformatics and NMR studies played a significant role in the development of our understanding of IDPs. Here the goal is to recount some of this history and to project from this experience possible directions for future work.