Computational Methods to Investigate Intrinsically Disordered Proteins and their Complexes

Abstract: In 1999 Wright and Dyson highlighted the fact that large sections of the proteome of all organisms are comprised of protein sequences that lack globular folded structures under physiological conditions. Since then the biophysics community has made significant strides in unraveling the intricate structural and dynamic characteristics of intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs). Unlike crystallographic beamlines and their role in streamlining acquisition of structures for folded proteins, an integrated experimental and computational approach aimed at IDPs/IDRs has emerged. In this Perspective we aim to provide a robust overview of current computational tools for IDPs and IDRs, and most recently their complexes and phase separated states, including statistical models, physics-based approaches, and machine learning methods that permit structural ensemble generation and validation against many solution experimental data types.