Intrinsically disordered proteins and biomolecular condensates as drug targets

Structural Protein Analysis of Driver Gene Mutations in Conjunctival Melanoma

“…To our knowledge, this is the first study to analyze the mutations associated with the pathogenesis of CM, namely for their IDPRs and the PPI network of each of these proteins. In recent years, there has been a push to target intrinsically disordered protein regions involved in various cancers including adenocarcinoma, Ewing's sarcoma, and lymphoma [27,41,42]. While targeting IDPRs is challenging as they are highly dynamic and have poorly defined structures, intrinsically disordered protein (IDP) drug discovery campaigns [43] are addressing these limitations.…”

Deep learning in prediction of intrinsic disorder in proteins

“…Numerous studies of IDPs reveal that they are crucial for a wide spectrum of cellular functions that include signaling, molecular recognition and assembly, cell cycle regulation, transcription, translation and phase separation [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] . Moreover, given their functional importance and prevalence in the human diseasome [12] , [20] , [21] , [22] , they serve as promising and currently underutilized leads for rational drug design efforts [23] , [24] , [25] , [26] , [27] .…”

“…Computational predictors already made large impact on the intrinsic disorder field, by powering a rapid acceleration in the research on IDPs and IDRs [35] . They are also used across many areas including rational drug design [23] , [24] , [25] , [26] , structural genomics [36] , [37] , [38] , and medicine [39] , [40] .…”

Low amounts of heavy water increase the phase separation propensity of a fragment of the androgen receptor activation domain

“…As a consequence of this there is substantial interest in investigating the structural properties of ID proteins in the interior of condensates, rather than in aqueous solution, because the physico‐chemical properties of these two environments can be quite different 5 . Specific issues that merit attention include, among others, investigating whether condensation can induce structure in otherwise ID proteins 6,7 and whether the strength of inter‐molecular interactions—including interactions with drug‐like molecules—is altered in condensates 8–10 . Answering these questions is important to better understand the roles that condensation plays in the regulation of biological functions and how it can contribute to the onset of disease—for example due to the presence of mutations—as well as to assess whether it will be possible to direct small molecules to therapeutic targets in biomolecular condensates 10 …”