Novel Strategies for Drug Discovery Based on Intrinsically Disordered Proteins (IDPs)

Abstract: Intrinsically disordered proteins (IDPs) are proteins that usually do not adopt well-defined native structures when isolated in solution under physiological conditions. Numerous IDPs have close relationships with human diseases such as tumor, Parkinson disease, Alzheimer disease, diabetes, and so on. These disease-associated IDPs commonly play principal roles in the disease-associated protein-protein interaction networks. Most of them in the disease datasets have more interactants and hence the size of the disease-associated IDPs interaction network is simultaneously increased. For example, the tumor suppressor protein p53 is an intrinsically disordered protein and also a hub protein in the p53 interaction network; α-synuclein, an intrinsically disordered protein involved in Parkinson diseases, is also a hub of the protein network. The disease-associated IDPs may provide potential targets for drugs modulating protein-protein interaction networks. Therefore, novel strategies for drug discovery based on IDPs are in the ascendant. It is dependent on the features of IDPs to develop the novel strategies. It is found out that IDPs have unique structural features such as high flexibility and random coil-like conformations which enable them to participate in both the “one to many” and “many to one” interaction. Accordingly, in order to promote novel strategies for drug discovery, it is essential that more and more features of IDPs are revealed by experimental and computing methods.