Recent advances in de novo computational design and redesign of intrinsically disordered proteins and intrinsically disordered protein regions

In the early 2000s, the concept of "unstructured biology"has emerged to be an important field in protein science by generating various new research directions. Many novel strategies and methods have been developed that are focused on effectively identifying/predicting intrinsically disordered proteins (IDPs) and intrinsically disordered protein regions (IDPRs), identifying their potential functions, disorder based drug design etc. Due to the range of functions of IDPs/IDPRs and their involvement in various debilitating diseases they are of contemporary interest to the scientific community. Recent researches are focused on designing/redesigning specific IDPs/IDPRs de novo. These de novo design/redesigns of IDPs/IDPRs are carried out by altering compositional biases and specific sequence patterning parameters. The main focus of these researches is to influence specific molecular functions, phase behavior, cellular phenotypes etc. In this review, we first provide the differences of natively folded and natively unfolded or IDPs with respect to their potential energy landscapes. Here, we provide current understandings on the different computational design strategies and methods that have been utilized in de novo design and redesigns of IDPs and IDPRs. Finally, we conclude the review by discussing the challenges that have been faced during the computational design/design attempts of IDPs/IDPRs.